Any feedback?
Information on EC 3.3.2.6 - leukotriene-A4 hydrolase and Organism(s) Homo sapiens and UniProt Accession P09960
for references in articles please use BRENDA:EC3.3.2.6Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.3.2.6 leukotriene-A4 hydrolaseIUBMB Comments
This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates (see EC 3.4.11.6, aminopeptidase B). It also converts leukotriene A4 into leukotriene B4, unlike EC 3.3.2.10, soluble epoxide hydrolase, which converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) .
Specify your search results
Word Map
- 3.3.2.6
-
5-lipoxygenase
-
arachidonic
- epoxide
- medicine
- leukocyte
- asthma
- bestatin
-
chemoattractant
-
eicosanoids
-
metalloenzyme
- flap
-
ionophore
-
alox5ap
-
tuberculous
-
transcellular
-
5-lipoxygenase-activating
- aminopeptidases
- captopril
-
lipoxins
- pro-gly-pro
- montelukast
- proline-glycine-proline
-
5-hete
- zileuton
- diagnostics
- pharmacology
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
lta4h, lta4 hydrolase, leukotriene a4 hydrolase, leukotriene a(4) hydrolase, leukotriene-a4 hydrolase, leukotriene a4 hydrolase/aminopeptidase, lta4-h, leukotriene-a4-hydrolase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
leukotriene A4 hydrolase
-
LTA4H
-
hydrolase, leukotriene A4
-
-
-
-
leukotriene A(4) hydrolase
-
-
-
-
leukotriene A4 hydrolase
leukotriene A4 hydrolase/aminopeptidase
-
-
-
-
LTA-4 hydrolase
-
-
-
-
LTA4 hydrolase
LTA4H
leukotriene A4 hydrolase
-
-
-
-
leukotriene A4 hydrolase
-
-
LTA4 hydrolase
-
-
-
-
LTA4H
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
leukotriene A4 + H2O = leukotriene B4
Asp375 acts as a critical determinant for the stereoselective introduction of the 12R-hydroxyl group, possibly assisted by Gln134 and thus the biological activity of leukotriene B4
leukotriene A4 + H2O = leukotriene B4
bifunctional enzyme acting as an epoxide hydrolase and also as an aminopeptidase
leukotriene A4 + H2O = leukotriene B4
His295, His299, Glu318, Glu271 are amino acids involved in metallic binding and epoxid hydrolase activity, additional Glu296 and Tyr383 are required for the aminopeptidase activity
-
leukotriene A4 + H2O = leukotriene B4
the aminopeptidase activity is dependent upon an unmodified cysteine residue, by modifying this cysteine with a small CH3S group it is possible to separate the two enzymatic activities, the aminopeptidase activity and epoxid hydrolase activity, from each other
-
leukotriene A4 + H2O = leukotriene B4
enzyme contains two partly overlapping active sites which influence each other
-
leukotriene A4 + H2O = leukotriene B4
mechanistic models, Glu271 is specifically required for the epoxid hydrolase activity and peptidase activity
-
leukotriene A4 + H2O = leukotriene B4
Ser415 plays a key role in regulating epoxid hydrolase activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of ether bond
hydrolysis of ether bond
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase
This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates [6] (see EC 3.4.11.6, aminopeptidase B). It also converts leukotriene A4 into leukotriene B4, unlike EC 3.3.2.10, soluble epoxide hydrolase, which converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) [5].
CAS REGISTRY NUMBER
COMMENTARY
90119-07-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
-
-
-
?
L-arginine-7-amido-4-methylcoumarine + H2O
L-arginine + 4-methylcoumarin-7-amine
an artificial substrate
-
-
?
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
L-alanine-7-amido-4-methylcoumarin + H2O
L-alanine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-Arg-L-Ala-L-Arg + H2O
?
-
bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides
-
-
?
L-arginine + H2O
?
-
the best proteinogenic amino acid recognized by the enzyme is L-arginine
-
-
?
L-arginine-7-amido-4-methylcoumarin + H2O
L-arginine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-glutamate-7-amido-4-methylcoumarin + H2O
L-glutamate + 7-amino-4-methylcoumarin
-
-
-
-
?
L-histidine-7-amido-4-methylcoumarin + H2O
L-histidine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-leucine-7-amido-4-methylcoumarin + H2O
L-leucine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-lysine-7-amido-4-methylcoumarin + H2O
L-lysine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-methionine-7-amido-4-methylcoumarin + H2O
L-methionine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-phenylalanine-7-amido-4-methylcoumarin + H2O
L-phenylalanine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-proline-7-amido-4-methylcoumarin + H2O
L-proline + 7-amino-4-methylcoumarin
-
-
-
-
?
L-serine-7-amido-4-methylcoumarin + H2O
L-serine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-tyrosine-7-amido-4-methylcoumarin + H2O
L-tyrosine + 7-amino-4-methylcoumarin
-
-
-
-
?
leukotriene A5 + H2O
?
-
i.e. 5(S)-trans-5,6-oxido-7,9-trans-11,14,17-cis-eicosatetraenoic acid
-
-
?
leukotriene A4 + H2O
leukotriene B4
biosynthesis of leukotriene B4
-
?
leukotriene A4 + H2O
leukotriene B4
biosynthesis of leukotriene B4
-
?
leukotriene A4 + H2O
leukotriene B4
biosynthesis of leukotriene B4
-
?
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
-
-
-
-
?
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
-
substrate for the epoxide hydrolase reaction, in addition LTA4H shows a peptidase activity
-
-
?
leukotriene A4 + H2O
leukotriene B4
-
-
696628, 696629, 696636, 696688, 697856, 698172, 699434, 707687, 707704, 708038, 708077, 708181, 708250, 731112, 731116, 731439, 731445, 731746, 731871, 732701
-
-
?
leukotriene A4 + H2O
leukotriene B4
-
-
i.e. LTB4, a powerful proinflammatory agent
-
?
leukotriene A4 + H2O
leukotriene B4
-
model for the binding of leukotriene A4 to the active site
mutants of Tyr378 are able to generate, not only leukotriene B4, but also (5S,12R)-dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, in a yield of about 20-30%
?
leukotriene A4 + H2O
leukotriene B4
-
one of the physiologically important processes in the arachidonic acid biosynthetic pathway, leukotriene B4 is a proinflammatory mediator which stimulates adhesion of circulating neutrophils to vascular endothelium and directs their migration towards sites of inflammation
-
?
leukotriene A4 + H2O
leukotriene B4
-
central enzyme in leukotriene B4 formation, it is likely to be involved in transcellular leukotriene formation
-
?
leukotriene A4 + H2O
leukotriene B4
-
leukotriene A4 hydrolase catalyzes the final step in the synthesis of leukotriene B4, a potent chemoattractant and proinflammatory eicosanoid
-
-
?
additional information
?
-
proline-glycine-proline (PGP) is a substrate for the enzyme's aminopeptidase (AP) activity
-
-
?
additional information
?
-
substrates docking and molecular dynamics simulations, interaction analysis. The binding cavity of LTA4H is formed by H299, H295, E318, and Zn2+. Residues R563 and K565 in the C-terminal domain of LTA4H are key residues involved in carboxylate recognition from endogenous substrates of the enzyme
-
-
?
additional information
?
-
the aminopeptidase binding site shares a similar structure to LTA4H at its ligand binding sites
-
-
?
additional information
?
-
-
the aminopeptidase binding site shares a similar structure to LTA4H at its ligand binding sites
-
-
?
additional information
?
-
-
neutrophil LTA4 hydrolase also converts LTA5 to LTB5, less efficiently than LTA4 to LTB4
-
-
?
additional information
?
-
-
either glutamic or glutamine moiety at amino acid 297 is required for full LTA4 hydrolase activity, free carboxylic acid of glutamic acid is essential for aminopeptidase
-
-
?
additional information
?
-
-
not: glycine-4-nitroanilide, glutamyl-4-nitroanilide, valine-4-nitroanilide
-
-
?
additional information
?
-
-
the aminopeptidase activity accepts a variety of substrates and certain arginyl di- and tri-peptides as well as p-nitroanilide derivates of Ala and Arg
-
-
?
additional information
?
-
-
possible proteolytic function of the enzyme may be limited to the extracellular space
-
-
?
additional information
?
-
-
no activity with L-Asn, L-Asp, L-Glu, Gly, L-Ile, L-Thr, L-Trp, L-Val, as well as D-amino acids
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
-
-
-
?
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
leukotriene A4 + H2O
leukotriene B4
biosynthesis of leukotriene B4
-
?
leukotriene A4 + H2O
leukotriene B4
biosynthesis of leukotriene B4
-
?
leukotriene A4 + H2O
leukotriene B4
biosynthesis of leukotriene B4
-
?
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
-
-
-
-
?
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
-
substrate for the epoxide hydrolase reaction, in addition LTA4H shows a peptidase activity
-
-
?
leukotriene A4 + H2O
leukotriene B4
-
-
-
-
?
leukotriene A4 + H2O
leukotriene B4
-
-
i.e. LTB4, a powerful proinflammatory agent
-
?
leukotriene A4 + H2O
leukotriene B4
-
one of the physiologically important processes in the arachidonic acid biosynthetic pathway, leukotriene B4 is a proinflammatory mediator which stimulates adhesion of circulating neutrophils to vascular endothelium and directs their migration towards sites of inflammation
-
?
leukotriene A4 + H2O
leukotriene B4
-
central enzyme in leukotriene B4 formation, it is likely to be involved in transcellular leukotriene formation
-
?
leukotriene A4 + H2O
leukotriene B4
-
leukotriene A4 hydrolase catalyzes the final step in the synthesis of leukotriene B4, a potent chemoattractant and proinflammatory eicosanoid
-
-
?
additional information
?
-
-
possible proteolytic function of the enzyme may be limited to the extracellular space
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zinc
Zn2+
Br-
-
stimulates peptidase and epoxide hydrolase activity (i.e. conversion of leukotriene A4 into leukotriene B4), SCN- most effective, followed by Cl- and Br-
Cl-
-
stimulates peptidase activity, not epoxide hydrolase activity (i.e. conversion of leukotriene A4 into leukotriene B4), SCN- most effective, followed by Cl- and Br-
Co2+
-
apoenzyme can be restored by addition of Co2+, peptidase activity exceeds that of enzyme reactivated with zinc
thiocyanate
-
stimulates peptidase and epoxide hydrolase activity (i.e. conversion of leukotriene A4 into leukotriene B4), SCN- most effective, followed by Cl- and Br-
Zinc
Zn2+
Zinc
the sequence that codes for the zinc-ion-binding motif is identical in the short-from and long-form enzyme mRNAs
Zn2+
the zinc ion is essential for both catalytic activities of LTA4H, it is coordinated by three amino acid residues (His295, His299, Glu318) located in the catalytic domain
Zn2+
zinc metalloenzyme, enzyme LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein
Zinc
-
catalytic zinc site with the signature HEXXH-(X)18-E, three zinc binding ligands: His295, His299 and Glu318
Zinc
-
zinc protein
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-amino-N-[4-(phenylmethoxy)phenyl]-3-[4-(1H-imidazole)]propanamide dihydrochloride
-
(2S)-2-amino-N-[4-(phenylmethoxy)phenyl]benzenepropanamide hydrochloride
-
(2S)-N-[4-(phenylmethoxy)phenyl]-2-pyrrolidinecarboxamide hydrochloride
-
(4S)-4-amino-4-(2-(1,3,4-triazolyl))-N-(4-phenoxyphenyl)butanamide trifluoroacetate
-
(4S)-4-amino-5-(1-phthalimido)-N-(4-phenoxyphenyl)pentanamide trifluoroacetate
-
(4S)-4-amino-5-(1H-pyrrol-1-yl)-N-(4-phenoxyphenyl)pentanamide bistrifluoroacetate
-
(4S)-4-amino-5-(2-thio-5-amino-1,3,4-thiadiazol-2-yl)-N-(4-phenoxyphenyl)pentanamide bistrifluoroacetate
-
(R)-5-(1,2-dithiolan-3-yl) pentanoic acid
i.e. alpha-lipoic acid, inhibits both activities of the enzyme at concentrations lower than 0.010 mM. The carboxylate group of alpha lipoic acid situates at 3 A from important residues R563 and K565 in the catalytic pocket of the protein, suggesting that alpha lipoic acid participates in electrostatic interactions with these residues
(S)-2-((2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido)-4-methylpentanoic acid
-
(S)-2-((S)-2-(2-(((R)-1-amino-2-phenylethyl)(hydroxy)phosphoryl)acetamido)-3-phenylpropanamido)-3-phenylpropanoic acid
RB3041, tight slow-binding LTA4H inhibitor
(S)-2-((S)-2-(2-(((R)-1-aminoethyl)(hydroxy)phosphoryl)acetamido)-3-(biphenyl-4-yl)propanamido)propanoic acid
RB3040, tight slow-binding LTA4H inhibitor
1-([4-[(1,3-benzothiazol-2-yl)oxy]phenyl]methyl)piperidine-4-carboxylic acid
i.e. JNJ-26993135
4'-O-methyl shogoal
a potent enzyme inhibitor, non-cytotoxic to normal cells
4-((R)-2-(4-(4-chlorophenoxy)phenoxymethyl)pyrrolidin-1-yl)-l-butyric acid
-
4-((S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl)-butyric acid
-
4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide
enzyme binding structure, overview
4-dimethylamino-N-[4-(phenylmethoxy)phenyl]-butanamide trifluoroacetate
-
4-[(2S)-2-([4-(4-chlorophenoxy)phenoxy]methyl)-1-pyrrolidinyl]butanoic acid
i.e. DG-051
acrolein
acrolein in cigarette smoke in part inhibits LTA4H peptidase activity
methyl 5-(1,2-dithiolan-3-yl) pentanoate
i.e. alpha-lipoic acid methyl ester or LAME
N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine
i.e. kelatorphan, potent inhibitor of Zn-metalloenzymes
N1-(2-carboxyethyl)-N5-(4-phenoxyphenyl)-L-glutamamide trifluoroacetate
-
N1-(2-hydroxyethyl)-N5-(4-phenoxyphenyl)-L-glutamamide trifluoroacetate
-
N1-(3-carboxypropyl)-N5-(4-phenoxyphenyl)-L-glutamamide trifluoroacetate
-
N1-(4-carboxybutyl)-N5-(4-phenoxyphenyl)-L-glutamamide bistrifluoroacetate
-
N5-[4-(N-methyl-N-phenylamino)phenyl]-L-glutamine methyl ester trifluoroacetate
-
N5-[4-[4-(1H-pyrrol-1-yl)phenoxy]phenyl]-L-glutamine hemitrifluoroacetate
-
sulindac sulfide
reduces LTA4H activity in HT29 CRC cells, thus lowering LTB4 levels and decreasing HT29 cell viability
(1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)-carbamic acid tert-butyl ester
-
-
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[(4-nitrobenzyl)sulfanyl]propanoic acid
-
-
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[(4-phenoxybenzyl)sulfanyl]propanoic acid
-
-
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[(4-propylbenzyl)sulfanyl]propanoic acid
-
-
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[[4-(trifluoromethoxy)benzyl]sulfanyl]propanoic acid
-
-
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[[4-(trifluoromethyl)benzyl]sulfanyl]propanoic acid
-
-
(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]-1-(1,2,4-oxadiazol-2(3H)-ylmethyl)piperidine
-
-
(2R)-3-(benzylsulfanyl)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-bromobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-chlorobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-cyanobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-ethoxybenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-ethylbenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-fluorobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-iodobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-methoxybenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(4-methylbenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[(biphenyl-4-ylmethyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[3-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[4-(1-methylethyl)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(3-sulfanylbutanoyl)amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(3-sulfanylpropanoyl)amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(4-sulfanylbutanoyl)amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(sulfanylacetyl)amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2R)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2R)-2-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
SA6541
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[4-(methoxysulfinyl)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2R)-3-[[4-(methylsulfanyl)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2S)-1-[(2R)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
-
5% inhibition at 1 mM
(2S)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
-
-
(2S)-4-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]butanoic acid
-
-
(2S,4R)-3-(2-methyl-3-sulfanylpropanoyl)-2-naphthalen-1-yl-1,3-thiazolidine-4-carboxylic acid
-
58% inhibition at 1 mM
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(2-phenylethyl)sulfanyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(3-phenylpropyl)sulfanyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(naphthalen-1-ylmethyl)sulfanyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(naphthalen-2-ylmethyl)sulfanyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-4-(benzylsulfanyl)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-4-[(2-methylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-4-[(3-methylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
-
-
(2S,4S)-4-[[4-(methylsulfanyl)benzyl]sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
-
-
(4R)-2-furan-2-yl-3-[(2S)-2-methyl-3-sulfanylpropanoyl]-1,3-thiazolidine-4-carboxylic acid
-
36% inhibition at 1 mM
(4R)-3-[(2R)-2-methyl-3-sulfanylpropanoyl]-1,3-thiazolidine-4-carboxylic acid
-
18% inhibition at 1 mM
(4R)-3-[(2S)-2-methyl-3-sulfanylpropanoyl]-1,3-thiazolidine-4-carboxylic acid
-
58% inhibition at 1 mM
(4R)-3-[(2S)-2-methyl-3-sulfanylpropanoyl]-2-pyridin-4-yl-1,3-thiazolidine-4-carboxylic acid
-
25% inhibition at 1 mM
(4R)-3-[(2S)-2-methyl-3-sulfanylpropanoyl]-2-thiophen-2-yl-1,3-thiazolidine-4-carboxylic acid
-
14% inhibition at 1 mM
(4R)-4-[[4-(1-methylethyl)benzyl]sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
-
-
(4S)-4-([2-[4-(1-methylethyl)phenyl]ethyl]sulfanyl)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
-
-
(4S)-4-([3-[4-(1-methylethyl)phenyl]propyl]sulfanyl)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
-
-
(4S)-4-[(4-cyclohexylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
-
-
(4S)-4-[(4-tert-butylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
-
-
(4S)-4-[[4-(1-methylethyl)benzyl]sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
-
-
1-(1-[2-[4-(1,3-benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(1-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)pyrrolidin-2-one
-
-
1-(2-(4-(2-(trifluoromethyl)phenoxy)phenoxy)ethyl)pyrrolidine
-
dual target inhibitor against cyclooxygenase COX-2 and leukotriene A4 hydrolyase in the enzyme assays and the human whole blood assay with IC50 values in the micromolar to submicromolar range. Inhibitor shows good selectivity for COX-2 over COX-1
1-(2-(4-(2-nitrophenoxy)phenoxy)ethyl)pyrrolidine
-
dual target inhibitor against cyclooxygenase COX-2 and leukotriene A4 hydrolyase in the enzyme assays and the human whole blood assay with IC50 values in the micromolar to submicromolar range. Inhibitor shows good selectivity for COX-2 over COX-1
1-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-2-[[4-(furan-2-yl)-5-hydroxy-4H-1,2,4-triazol-3-yl]sulfanyl]ethanone
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
1-(5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[5-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[5-([1,3]thiazolo[4,5-c]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[5-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[6-([1,3]thiazolo[4,5-c]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-(5-[[6-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
-
-
1-[1-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]piperidin-4-yl]pyrrolidin-2-one
-
-
1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidine-4-carboxylic acid amide
-
-
1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidine-4-carboxylic acid amide
-
-
1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]piperidine-4-carboxamide
-
-
1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]piperidine-4-carboxamide
-
-
1-[5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]ethanone
-
-
1-[5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]ethanone
-
-
1-[5-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]ethanone
-
-
1-[5-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]ethanone
-
-
1-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]piperidine-4-carboxylic acid
-
-
1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidine-4-carboxylic acid
-
-
2,3-Butanedione
-
preincubation with bestatin partially protects enzyme from inactivation
2,4-dimethyl-N-[[2-(thiophen-2-yl)-1,3-thiazol-4-yl]methyl]-1,3-thiazole-5-sulfonamide
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
2-bromo-4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
-
-
2-fluoro-4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
-
-
2-[4-(2-morpholin-4-ylethoxy)phenoxy]-1-(2-trimethylsilanylethoxymethyl)-1H-benzoimidazole
-
-
2-[[2-(piperidin-1-ylmethyl)-1-benzofuran-5-yl]oxy][1,3]thiazolo[4,5-b]pyridine
-
-
2-[[2-(piperidin-1-ylmethyl)-1-benzofuran-6-yl]oxy][1,3]thiazolo[4,5-b]pyridine
-
-
2-[[3-(morpholin-4-ylmethyl)-1-benzofuran-6-yl]oxy][1,3]thiazolo[4,5-b]pyridine
-
-
2-[[3-(piperidin-1-ylmethyl)-1-benzofuran-6-yl]oxy][1,3]thiazolo[4,5-b]pyridine
-
-
2-[[4-methyl-5-([[2-oxo-2-(phenylamino)ethyl]sulfanyl]methyl)-4H-1,2,4-triazol-3-yl]sulfanyl]-N-phenylacetamide
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
3-(1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)oxazolidin-2-one
-
-
3-(1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-yl)oxazolidin-2-one
-
-
3-(4-fluorophenyl)-5-[2-methyl-5-(pyrrolidin-1-ylsulfonyl)furan-3-yl]-1,2,4-oxadiazole
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
3-fluoro-4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
-
-
3-[[4-(1-methylethyl)benzyl]sulfanyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-valine
-
-
4-([(1R,5S)-3-[(4-benzylphenyl)amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl)benzoic acid
-
-
4-([(1R,5S)-3-[(4-phenoxyphenyl)amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl)benzoic acid
-
-
4-([(2R)-2-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]pyrrolidin-1-yl]methyl)benzoic acid
-
-
4-([2-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]pyrrolidin-1-yl]methyl)benzoic acid
-
-
4-([4-[([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)methyl]piperidin-1-yl]methyl)benzoic acid
-
-
4-([methyl[2-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)ethyl]amino]methyl)benzoic acid
-
-
4-([methyl[2-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)ethyl]amino]methyl)benzoic acid
-
-
4-([methyl[3-([2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl]amino]methyl)benzoic acid
-
-
4-([methyl[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)propyl]amino]methyl)benzoic acid
-
-
4-([methyl[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)cyclohexyl]amino]methyl)benzoic acid
-
-
4-([[2,2-dimethyl-3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl](methyl)amino]methyl)benzoic acid
-
-
4-([[3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl]amino]methyl)benzoic acid
-
-
4-([[3-([2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl]amino]methyl)benzoic acid
-
-
4-([[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)cyclohexyl]amino]methyl)benzoic acid
-
-
4-[(2S)-2-([4-[4-(thiophen-3-yl)benzyl]phenoxy]methyl)piperidin-1-yl]butanoic acid
-
-
4-[(2S)-2-[[4-(4-chloro-2-hydroxyphenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid
-
i.e. DG-051 M1-A, a derivative derived from DG-051
4-[(2S)-2-[[4-(4-chloro-3-hydroxyphenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid
-
i.e. DG-051 M1-B, a derivative derived from DG-051
4-[(2S)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]-1-oxidopyrrolidin-1-yl]butanoic acid
-
i.e. DG-051 M2, an N-oxide derivative derived from DG-051
4-[(4-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]-1,4-diazepan-1-yl)methyl]benzoic acid
-
-
4-[(4-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperazin-1-yl)methyl]benzoic acid
-
-
4-[(5-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]benzoic acid
-
-
4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]-3-nitrobenzoic acid
-
-
4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]cyclohexanecarboxylic acid
-
-
4-[(methyl[[(2R)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperidin-2-yl]methyl]amino)methyl]benzoic acid
-
-
4-[(methyl[[(2R)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]pyrrolidin-2-yl]methyl]amino)methyl]benzoic acid
-
-
4-[(methyl[[(2S)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperidin-2-yl]methyl]amino)methyl]benzoic acid
-
-
4-[(methyl[[(2S)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]pyrrolidin-2-yl]methyl]amino)methyl]benzoic acid
-
-
4-[2-[(1R,5S)-3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]ethyl]benzoic acid
-
-
4-[2-[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]ethyl]benzoic acid
-
-
4-[2-[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]ethyl]benzoic acid
-
-
4-[[(1R,5S)-3-([4-[3-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
JNJ-26993135
4-[[(1R,5S)-3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-([4-[4-(1,3-thiazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-([4-[4-(1H-pyrrol-1-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-([4-[4-(trifluoromethyl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(1,3-benzothiazol-2-yloxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(2-chlorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(2-fluorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(4-chlorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(4-fluorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(4-methoxyphenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(benzyloxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(biphenyl-4-yloxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(1R,5S)-3-[[4-(pyridin-4-ylmethyl)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
-
-
4-[[(3-[[2-([4-[(2R)-2-hydroxy-2-phenylethoxy]phenyl]amino)-2-oxoethyl](methyl)amino]propyl)(methyl)amino]methyl]benzoic acid
-
-
4-[[(3R)-3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)pyrrolidin-1-yl]methyl]benzoic acid
-
-
4-[[(3S)-3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)pyrrolidin-1-yl]methyl]benzoic acid
-
-
4-[[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]methyl]benzoic acid
-
-
4-[[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)pyrrolidin-1-yl]methyl]benzoic acid
-
-
4-[[4-(1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]hydrazino)piperidin-1-yl]methyl]benzoic acid
-
-
4-[[4-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)azepan-1-yl]methyl]benzoic acid
-
-
4-[[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)azepan-1-yl]methyl]benzoic acid
-
-
4-[[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]methyl]benzoic acid
-
-
4-[[methyl(1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]azepan-4-yl)amino]methyl]benzoic acid
-
-
4-[[methyl(1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperidin-4-yl)amino]methyl]benzoic acid
-
-
4-[[methyl(3-[methyl[2-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-2-oxoethyl]amino]propyl)amino]methyl]benzoic acid
-
-
4-[[[3-[(2-[[4-(2-fluorophenoxy)phenyl]amino]-2-oxoethyl)(methyl)amino]propyl](methyl)amino]methyl]benzoic acid
-
-
4-[[[3-[(2-[[4-(4-chlorophenoxy)phenyl]amino]-2-oxoethyl)(methyl)amino]propyl](methyl)amino]methyl]benzoic acid
-
-
4-[[[3-[(2-[[4-(4-fluorophenoxy)phenyl]amino]-2-oxoethyl)(methyl)amino]propyl](methyl)amino]methyl]benzoic acid
-
-
4-[[[3-[[2-[(4-benzylphenyl)amino]-2-oxoethyl](methyl)amino]propyl](methyl)amino]methyl]benzoic acid
-
-
5-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]furan-2-carboxylic acid
-
-
acetic acid (1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-ylcarbamoyl)methyl ester
-
-
acetic acid [1-[4-(benzothiazol-2-yloxy)benzyl]piperidin-4-ylcarbamoyl]methyl ester
-
-
Acetic anhydride
-
complete loss of peptidase activity and epoxide hydrolase activity
citraconic anhydride
-
complete loss of peptidase activity and epoxide hydrolase activity
diamide/glutathione combination
-
complete loss of peptidase activity and epoxide hydrolase activity
-
leukotriene A4 ethyl ester
-
comparison of inactivation of wild-type and mutant enzymes
methyl methanethiosulfonate
-
inhibition of epoxide hydrolase activity, stimulation of peptidase activity
methyl-methane thiosulfonate
-
inhibits aminopeptidase activity and NaCl stimulates this inactivation, beta-mercaptoethanol reactivates this inactivation, bestatin protects inactivation, little effect on epoxid hydrolase activity
N-(1-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)acetamide
-
-
N-(1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)acetamide
-
-
N-(2-[[6-(4-fluorophenyl)pyridazin-3-yl]amino]ethyl)-1,2-dimethyl-1H-imidazole-4-sulfonamide
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
N-(8-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]-8-azabicyclo[3.2.1]oct-3-yl)acetamide
-
-
N-(8-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]-8-azabicyclo[3.2.1]oct-3-yl)acetamide
-
-
N-Acetylimidazole
-
75 min, loss of 92% peptidase activity and 78% of epoxide hydrolase activity, both activities are restored by hydroxylamine and bestatin protects
N-[(3-endo)-8-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]-8-azabicyclo[3.2.1]oct-3-yl]acetamide
-
-
N-[(3-endo)-8-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-8-azabicyclo[3.2.1]oct-3-yl]acetamide
-
-
N-[2-[(furan-2-ylmethyl)sulfanyl]ethyl]-2-[[1-(4-hydroxyphenyl)-1H-tetrazol-5-yl]sulfanyl]acetamide
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
N-[3-[3-(acetylamino)phenoxy]propyl]-3-[3-(pyridin-2-yl)-1,2,4-oxadiazol-5-yl]propanamide
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
N-[4-(3-chlorophenyl)-2,5-dioxopiperazin-1-yl]-2-[[4-methyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]acetamide
-
compound identified by pharmacophore modeling, binds both human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S with good binding characteristics
N-[8-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]-8-azabicyclo[3.2.1]oct-3-yl]acetamide
-
-
N2-methyl-N2-[3-[methyl(4-oxobutyl)amino]propyl]-N-(4-phenoxyphenyl)glycinamide
-
-
N2-methyl-N2-[4-[methyl(4-oxobutyl)amino]butyl]-N-(4-phenoxyphenyl)glycinamide
-
-
S-(4-cyclohexylbenzyl)-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[(4-cyclohexylphenyl)(phenyl)methyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[1-(4-cyclohexylphenyl)-1-methylethyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[1-methyl-1-[4-(1-methylethyl)phenyl]ethyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[1-[4-(1-methylethyl)phenyl]butyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[1-[4-(1-methylethyl)phenyl]ethyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[1-[4-(1-methylethyl)phenyl]pentyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[1-[4-(1-methylethyl)phenyl]propyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[2-methyl-1-[4-(1-methylethyl)phenyl]propyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
S-[[4-(1-methylethyl)phenyl](phenyl)methyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
-
-
Trinitrobenzenesulfonate
-
complete loss of peptidase activity and epoxide hydrolase activity
4-[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid
i.e. DG-051
4-[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid
i.e. DG051
bestatin
isolated from Streptomyces olivoreticuli, a general AP inhibitor, inhibits LTB4 biosynthesis. Treatment with bestatin inhibits cell proliferation of lung carcinoma A549 cells by significantly reducing LTA4H activity
bestatin
significantly inhibits LTB4 production, samples from13 CRC patients show a significant decrease in LTB4, the LTA4H signaling pathway, and Ki-67 in the bestatin-treated group compared with the untreated group
resveratrol
binds directly to LTA4H and inhibits its activity. The antiproliferative effect of resveratrol is decreased in LTA4H mRNA knockdown cells, LTA4H is a direct target of resveratrol
[6]-gingerol
from ginger, [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA4H activity in HCT116 colorectal cancer cells, overview. [6]-Gingerol specifically binds with LTA4H in vitro and ex vivo
1-[4-(1,3-benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid
-
JNJ-27265732
2-oxo-3-amino carboxylic esters
-
contain a transition state mimic of the enzyme-catalyzed amide cleavage as a core and additional complementary components which resemble the hydrophobic nature of the conjugated polyene system of the natural substrate LTA4
-
4-[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid
-
i.e. DG-051, a phase II clinical candidate
DG-051
-
a LTA4H inhibitor, used for therapeutic modulation of the leukotriene synthesis pathway in case of myocardial infarction
leukotriene A4
-
suicide inactivation via an apparently mechanism-based irreversible binding of leukotriene A4 to the protein in a 1:1 stoichiometry, comparison of inactivation of wild-type and mutant enzymes, Tyr378 is a residue, which is involved in the binding of leukotriene A4
leukotriene A4
-
leukotriene A4 binds covalently to Tyr378 and blocks epoxide hydrolase and aminopeptidase activities
leukotriene A4
-
pre-treatment of enzyme by methyl-methane thiosulfonate does not protect against suicide inactivation by leukotriene A4
leukotriene A4 methyl ester
-
comparison of inactivation of wild-type and mutant enzymes
N-[1-[4-(1,3-benzothiazol-2-yloxy)benzyl]piperidin-4-yl]-2-hydroxyacetamide
-
SC-57461A
additional information
structure-based drug discovery, inhibitor binding and molecular docking, overview
-
additional information
5-lipoxygenase inhibitor zileuton, or the 5-lipoxygenase activating protein inhibitor MK-886, are unable to inhibit the activity of the enzyme. Inhibitor docking and molecular dynamics simulations, interaction analysis
-
additional information
drug repurposing of histone deacetylase (HDAC) inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis, overview. Analysis of potential inhibitors of LTA4H across a panel of 18 HDAC inhibitors, using enzymatic assay, thermofluor assay, and X-ray crystallographic investigation. Detailed mechanisms of down-regulation of proinflammatory cytokines by SAHA or M344 are determined in vivo. Cotreatment of N-(6-(2-aminophenylamino)-6-oxyhexyl)-4-methylbenzamide and (S)-2-((2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido)-4-methylpentanoic acid synergistically represses the migration of neutrophil and LTB4-induced neutrophil migration is not affected by these treatments. Molecular modelling of HDAC inhibitors against LTA4H hydrolase and aminopeptidase
-
additional information
-
drug repurposing of histone deacetylase (HDAC) inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis, overview. Analysis of potential inhibitors of LTA4H across a panel of 18 HDAC inhibitors, using enzymatic assay, thermofluor assay, and X-ray crystallographic investigation. Detailed mechanisms of down-regulation of proinflammatory cytokines by SAHA or M344 are determined in vivo. Cotreatment of N-(6-(2-aminophenylamino)-6-oxyhexyl)-4-methylbenzamide and (S)-2-((2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido)-4-methylpentanoic acid synergistically represses the migration of neutrophil and LTB4-induced neutrophil migration is not affected by these treatments. Molecular modelling of HDAC inhibitors against LTA4H hydrolase and aminopeptidase
-
additional information
synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of gingerol derivatives as potential colorectal cancer therapy. NMR spectroscopic structure analysis, enzyme-inhibitor interactions, molecular modeling and docking study, overview. IC50 for cytotoxicity with HCT-116, TIG-1, and HF-1 cells
-
additional information
-
synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of gingerol derivatives as potential colorectal cancer therapy. NMR spectroscopic structure analysis, enzyme-inhibitor interactions, molecular modeling and docking study, overview. IC50 for cytotoxicity with HCT-116, TIG-1, and HF-1 cells
-
additional information
thermodynamic properties of structurally distinct leukotriene A4 hydrolase inhibitors. An in silico method for the determination of stabilized water molecules in the binding site of the apo structure of LTA4H is used to interpret the measured thermodynamic data and provided insights for design of novel LTA4H inhibitors. Fluorescence-based assay system with recombinant His6-tagged enzyme is used for determination of the inhibition kinetics
-
additional information
tosedostat, or CHR-2797 shows inhibition of the aminopeptidase activity. [6]-Gingerol and derivatives show chemopreventive effects and selective cytotoxicity toward HCT-116 cells but not toward healthy cells
-
additional information
-
some enzyme inhibitors also affect the cytotoxicity of the anthrax lethal factor on macrophage cell lines
-
additional information
-
leukotriene A4 inhibitors based on piperidine and piperazine scaffolds, overview
-
additional information
-
combined molecular docking and pharmacophore filtering assay for identification of chemical compounds that can simultaneously inhibit the human leukotriene hydrolase hLTA4H and the human leukotriene C4 synthase hLTC4S enzymes
-
additional information
-
not inhibited by NI101, 2-(5-(benzyloxy)-1H-indol-3-yl)ethanaminium chloride, 2-(5-(naphthalen-2-ylmethoxy)-1H-indol-3-yl)ethanaminiumchloride, 2-(5-(naphthalen-1-ylmethoxy)-1H-indol-3-yl)ethanaminium chloride, 2-(5-(3-phenoxybenzyloxy)-1H-indol-3-yl)ethanaminium chloride, 2-(5-(2-(4-(4-nitrophenoxy)phenoxy)ethoxy)-1H-indol-3-yl)ethanaminium chloride, 2-(5-(2-(4-(2-nitrophenoxy)phenoxy)ethoxy)-1H-indol-3-yl) ethanaminium chloride, 3-(2-(5-(3-phenoxybenzyloxy)-1H-indol-3-yl)ethylamino)propanoic acid, and 3-(2-(5-(2-(4-phenoxyphenoxy)ethoxy)-1H-indol-3-yl) ethylamino)propanoic acid
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.3
Arg-Ser-Arg
wild type enzyme, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
0.006 - 0.028
leukotriene A4
pH 8.0, wild-type enzyme in comparison to mutant enzymes
0.301
L-arginine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
1.9
L-Ala-p-nitroanilide
mutant enzyme E296Q, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
1.9
L-Ala-p-nitroanilide
wild type enzyme, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
3
L-Ala-p-nitroanilide
mutant enzyme D375A, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
1.5
L-Arg-p-nitroanilide
wild type enzyme, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
2.2
L-Arg-p-nitroanilide
mutant enzyme E296Q, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
0.006 - 0.028
leukotriene A4
-
pH 8.0, wild-type enzyme in comparison to mutant enzymes
additional information
additional information
-
influence of NaCl and NaSCN on KM
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.56
Arg-Ser-Arg
wild type enzyme, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
0.21 - 0.47
leukotriene A4
pH 8.0, wild-type enzyme in comparison to mutant enzymes
0.001
L-Ala-p-nitroanilide
mutant enzyme E296Q, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
0.5
L-Ala-p-nitroanilide
mutant enzyme D375A, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
1.7
L-Ala-p-nitroanilide
wild type enzyme, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
0.002
L-Arg-p-nitroanilide
mutant enzyme E296Q, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
1.9
L-Arg-p-nitroanilide
wild type enzyme, 500 mM KCl in 250 mM Tris buffer (pH 7.5)
0.21 - 0.47
leukotriene A4
-
pH 8.0, wild-type enzyme in comparison to mutant enzymes
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.497
L-alanine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
0.4706
L-arginine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
0.343
L-leucine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
0.617
L-lysine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
0.298
L-methionine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% of bovine serum albumin, at 37°C
0.747
L-phenylalanine-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
0.449
L-proline-7-amido-4-methylcoumarin
-
in 250 mM Tris buffer, pH 7.5, containing 500 mM KCl and 0.1% (w/v) of bovine serum albumin, at 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0058
(2S)-2,6-diamino-N-[4-(phenylmethoxy)phenyl]hexanamide dihydrochloride
Homo sapiens
-
0.00013
(2S)-2-amino-5-oxo-5-[(4-phenoxyphenyl)amino]-1-pentanesulfonic acid
Homo sapiens
-
0.01
(2S)-2-amino-N-[4-(phenylmethoxy)phenyl]-3-[4-(1H-imidazole)]propanamide dihydrochloride
Homo sapiens
-
0.00015
(2S)-2-amino-N-[4-(phenylmethoxy)phenyl]-propanamide hydrochloride
Homo sapiens
-
0.002
(2S)-2-amino-N-[4-(phenylmethoxy)phenyl]benzenepropanamide hydrochloride
Homo sapiens
IC50 above 0.002 mM
0.002
(2S)-N-[4-(phenylmethoxy)phenyl]-2-pyrrolidinecarboxamide hydrochloride
Homo sapiens
IC50 above 0.002 mM
0.002
(2S,3S)-2-amino-3-methyl-N-[4-(phenylmethoxy)-phenyl]pentanamide
Homo sapiens
IC50 above 0.002 mM
0.00074
(4S)-4-amino-4-(2-(1,3,4-triazolyl))-N-(4-phenoxyphenyl)butanamide trifluoroacetate
Homo sapiens
-
0.000085
(4S)-4-amino-5-(1-phthalimido)-N-(4-phenoxyphenyl)pentanamide trifluoroacetate
Homo sapiens
-
0.00039
(4S)-4-amino-5-(1H-pyrrol-1-yl)-N-(4-phenoxyphenyl)pentanamide bistrifluoroacetate
Homo sapiens
-
0.00035
(4S)-4-amino-5-(2-thio-5-amino-1,3,4-thiadiazol-2-yl)-N-(4-phenoxyphenyl)pentanamide bistrifluoroacetate
Homo sapiens
-
0.000011
1-([4-[(1,3-benzothiazol-2-yl)oxy]phenyl]methyl)piperidine-4-carboxylic acid
Homo sapiens
pH and temperature not specified in the publication
0.000047
4-((S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl)-butyric acid
Homo sapiens
-
0.0005
4-(4-benzylphenyl)-1,3-thiazol-2-amine
Homo sapiens
pH and temperature not specified in the publication
0.00068
4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide
Homo sapiens
pH and temperature not specified in the publication
0.0094
4-dimethylamino-N-[4-(phenylmethoxy)phenyl]-butanamide trifluoroacetate
Homo sapiens
-
0.011
4-methylamino-N-[4-(phenylmethoxy)phenyl]butanamide trifluoroacetate
Homo sapiens
-
0.000047
4-[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.018
5-oxo-5-[[4-(phenylmethoxy)phenyl]amino]pentanoic acid
Homo sapiens
IC50 above 0.018 mM
0.01
abexinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
belinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
entinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
givinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
JNJ-26481585
Homo sapiens
above, pH and temperature not specified in the publication
0.01
mocetinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
N-(6-(2-aminophenylamino)-6-oxyhexyl)-4-methylbenzamide
Homo sapiens
above, pH and temperature not specified in the publication
0.00017
N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine
Homo sapiens
pH 8.0, temperature not specified in the publication
0.000025
N-[3-(4-benzylphenoxy)propyl]-N-methyl-beta-alanine
Homo sapiens
pH and temperature not specified in the publication
0.000022
N1-(2-aminoethyl)-N5-(4-phenoxyphenyl)-L-glutamamide hydrochloride
Homo sapiens
-
0.000022
N1-(2-carboxyethyl)-N5-(4-phenoxyphenyl)-L-glutamamide trifluoroacetate
Homo sapiens
-
0.00002
N1-(2-hydroxyethyl)-N5-(4-phenoxyphenyl)-L-glutamamide trifluoroacetate
Homo sapiens
-
0.000017
N1-(3-carboxypropyl)-N5-(4-phenoxyphenyl)-L-glutamamide trifluoroacetate
Homo sapiens
-
0.000019
N1-(4-carboxybutyl)-N5-(4-phenoxyphenyl)-L-glutamamide bistrifluoroacetate
Homo sapiens
-
0.000025
N1-hydroxy-N5-[4-(phenylmethoxy)phenyl]-L-glutamamide trifluoroacetate
Homo sapiens
-
0.002
N1-[4-(phenylmethoxy)phenyl]-L-glutamamide hydrochloride
Homo sapiens
IC50 above 0.002 mM
0.000017
N5-[4-(2-hydroxy-3-phenylpropoxy)phenyl]-L-glutamine trifluoroacetate
Homo sapiens
-
0.000018
N5-[4-(2-oxo-3-phenylpropoxy)phenyl]-L-glutamine trifluoroacetate
Homo sapiens
-
0.000029
N5-[4-(4-(3-furyl)phenoxy)phenyl]-L-glutamamide trifluoroacetate
Homo sapiens
-
0.008
N5-[4-(N-methyl-N-phenylamino)phenyl]-L-glutamine methyl ester trifluoroacetate
Homo sapiens
-
0.00006
N5-[4-(phenylmethoxy)phenyl]-L-glutamine 1,1-dimethylethyl ester
Homo sapiens
-
0.000039
N5-[4-(phenylmethoxy)phenyl]-L-glutamine methyl ester hydrochloride
Homo sapiens
-
0.018
N5-[4-methoxyphenyl]-L-glutamine methyl ester trifluoroacetate
Homo sapiens
IC50 above 0.018 mM
0.000022
N5-[4-[4-(1H-pyrrol-1-yl)phenoxy]phenyl]-L-glutamine hemitrifluoroacetate
Homo sapiens
-
0.000006
N6-[4-(4-methylphenoxy)phenyl]-L-homoglutamine trifluoroacetate
Homo sapiens
-
0.01
panobinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
pracinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
resminostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
rocilinostat
Homo sapiens
above, pH and temperature not specified in the publication
0.01
scriptaid
Homo sapiens
above, pH and temperature not specified in the publication
0.00765
suberanilohydroxamic acid
Homo sapiens
pH and temperature not specified in the publication
-
0.01
trichostatin A
Homo sapiens
above, pH and temperature not specified in the publication
0.01
Valproate
Homo sapiens
above, pH and temperature not specified in the publication
0.000014
(1-[2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)methanol
Homo sapiens
-
-
0.000013
(1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)-methanol
Homo sapiens
-
-
0.0049
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[(4-nitrobenzyl)sulfanyl]propanoic acid
Homo sapiens
-
-
0.0017
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[(4-phenoxybenzyl)sulfanyl]propanoic acid
Homo sapiens
-
-
0.000072
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[(4-propylbenzyl)sulfanyl]propanoic acid
Homo sapiens
-
-
0.0004
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[[4-(trifluoromethoxy)benzyl]sulfanyl]propanoic acid
Homo sapiens
-
-
0.00014
(2R)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]-3-[[4-(trifluoromethyl)benzyl]sulfanyl]propanoic acid
Homo sapiens
-
-
0.0000069
(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]-1-(1,2,4-oxadiazol-2(3H)-ylmethyl)piperidine
Homo sapiens
-
-
0.01
(2R)-3-(benzylsulfanyl)-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.00061
(2R)-3-[(4-bromobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.0017
(2R)-3-[(4-chlorobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.00053
(2R)-3-[(4-cyanobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.00064
(2R)-3-[(4-ethoxybenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.00028
(2R)-3-[(4-ethylbenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.01
(2R)-3-[(4-fluorobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.000015
(2R)-3-[(4-iodobenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.0024
(2R)-3-[(4-methoxybenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.0072
(2R)-3-[(4-methylbenzyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.0006
(2R)-3-[(biphenyl-4-ylmethyl)sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.01
(2R)-3-[[3-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.0002
(2R)-3-[[4-(1-methylethyl)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.0074
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(3-sulfanylbutanoyl)amino]propanoic acid
Homo sapiens
-
-
0.01
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(3-sulfanylpropanoyl)amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.01
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(4-sulfanylbutanoyl)amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.00047
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[(sulfanylacetyl)amino]propanoic acid
Homo sapiens
-
-
0.0015
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2R)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.01
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2R)-2-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.00027
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.01
(2R)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.00016
(2R)-3-[[4-(methoxysulfinyl)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.000046
(2R)-3-[[4-(methylsulfanyl)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
-
0.01
(2S)-3-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]propanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.01
(2S)-4-[[4-(dimethylamino)benzyl]sulfanyl]-2-[[(2S)-2-methyl-3-sulfanylpropanoyl]amino]butanoic acid
Homo sapiens
-
IC50 above 0.01 mM
0.0051
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(2-phenylethyl)sulfanyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.0011
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(3-phenylpropyl)sulfanyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.0092
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(naphthalen-1-ylmethyl)sulfanyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.0011
(2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-[(naphthalen-2-ylmethyl)sulfanyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.0036
(2S,4S)-4-(benzylsulfanyl)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.00084
(2S,4S)-4-[(2-methylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.01
(2S,4S)-4-[(3-methylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
IC50 above 0.01 mM
0.00012
(2S,4S)-4-[[4-(methylsulfanyl)benzyl]sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Homo sapiens
-
-
0.00029
(4R)-4-[[4-(1-methylethyl)benzyl]sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
Homo sapiens
-
-
0.00079
(4S)-4-([2-[4-(1-methylethyl)phenyl]ethyl]sulfanyl)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
Homo sapiens
-
-
0.0027
(4S)-4-([3-[4-(1-methylethyl)phenyl]propyl]sulfanyl)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
Homo sapiens
-
-
0.000034
(4S)-4-[(4-cyclohexylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
Homo sapiens
-
-
0.000031
(4S)-4-[(4-tert-butylbenzyl)sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
Homo sapiens
-
-
0.000052
(4S)-4-[[4-(1-methylethyl)benzyl]sulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-proline
Homo sapiens
-
-
0.00007
1'-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl][1,4']bipiperidinyl-2-one
Homo sapiens
-
-
0.000016
1-(1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)pyrrolidin-2-one
Homo sapiens
-
-
0.000013
1-(1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-yl)pyrrolidin-2-one
Homo sapiens
-
-
0.000006
1-(1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]piperidin-4-yl)pyrrolidin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.000014
1-(1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]piperidin-4-yl)pyrrolidin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.000058
1-(1-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)pyrrolidin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.000003
1-(1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)pyrrolidin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00022
1-(2-(4-(2-(trifluoromethyl)phenoxy)phenoxy)ethyl)pyrrolidine
Homo sapiens
-
pH 7.4, 37°C
0.000007
1-(5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000014
1-(5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000007
1-(5-[[5-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.00034
1-(5-[[5-([1,3]thiazolo[4,5-c]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.00034
1-(5-[[5-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000034
1-(5-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.0000073 - 0.000062
1-(5-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
0.00034 - 0.00237
1-(5-[[6-([1,3]thiazolo[4,5-c]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
0.0003 - 0.00213
1-(5-[[6-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
0.000012
1-[1-[4-(benzothiazol-2-yloxy)benzyl]piperidin-4-yl]pyrrolidin-2-one
Homo sapiens
-
-
0.000049
1-[1-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]piperidin-4-yl]pyrrolidin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.000066
1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]-4-phenylpiperidin-4-ol
Homo sapiens
-
-
0.000013
1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidine-4-carboxylic acid amide
Homo sapiens
-
-
0.000028
1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidine-4-carboxylic acid amide
Homo sapiens
-
-
0.000016
1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]piperidine-4-carboxamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
1-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]piperidine-4-carboxamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000017
1-[4-(1,3-benzothiazol-2-yloxy)benzyl]piperidine-4-carboxamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
1-[4-(1,3-benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000017
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid amide
Homo sapiens
-
-
0.000006
1-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]piperidine-4-carboxamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000733
1-[4-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)benzyl]piperidine-4-carboxamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000007
1-[5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000006
1-[5-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000053
1-[5-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.00003
1-[5-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000014
1-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0000083
1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.015
2-(5-(2-(4-phenoxyphenoxy)ethoxy)-1H-indol-3-yl)ethanaminium chloride
Homo sapiens
-
in 10 mM sodium phosphate, pH 7.4, at 37°C
0.018
2-(5-(4-phenylbenzyloxy)-1H-indol-3-yl)ethanaminium chloride
Homo sapiens
-
in 10 mM sodium phosphate, pH 7.4, at 37°C
0.00001
2-bromo-4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000006
2-fluoro-4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000003
2-[4-(piperidin-1-ylmethyl)phenoxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.0018
2-[4-(piperidin-1-ylmethyl)phenoxy][1,3]thiazolo[4,5-c]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000614
2-[4-(piperidin-1-ylmethyl)phenoxy][1,3]thiazolo[5,4-c]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000008
2-[4-[2-(piperidin-1-yl)ethoxy]phenoxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000003
2-[4-[2-(piperidin-1-yl)ethyl]phenoxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.00033
2-[[2-(piperidin-1-ylmethyl)-1-benzofuran-5-yl]oxy]-1,3-benzothiazole
Homo sapiens
-
pH and temperature not specified in the publication
0.000066
2-[[2-(piperidin-1-ylmethyl)-1-benzofuran-5-yl]oxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.00043
2-[[2-(piperidin-1-ylmethyl)-1-benzofuran-6-yl]oxy]-1,3-benzothiazole
Homo sapiens
-
pH and temperature not specified in the publication
0.000051
2-[[2-(piperidin-1-ylmethyl)-1-benzofuran-6-yl]oxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.00014
2-[[3-(morpholin-4-ylmethyl)-1-benzofuran-6-yl]oxy]-1,3-benzothiazole
Homo sapiens
-
pH and temperature not specified in the publication
0.000025
2-[[3-(morpholin-4-ylmethyl)-1-benzofuran-6-yl]oxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000067
2-[[3-(piperidin-1-ylmethyl)-1-benzofuran-6-yl]oxy]-1,3-benzothiazole
Homo sapiens
-
pH and temperature not specified in the publication
0.0000046
2-[[3-(piperidin-1-ylmethyl)-1-benzofuran-6-yl]oxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
3-(1-[2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]piperidin-4-yl)oxazolidin-2-one
Homo sapiens
-
-
0.000029
3-(1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-yl)oxazolidin-2-one
Homo sapiens
-
-
0.0038
3-(2-(5-(4-phenylbenzyloxy)-1H-indol-3-yl)ethylamino)propanoic acid
Homo sapiens
-
in 10 mM sodium phosphate, pH 7.4, at 37°C
0.000007
3-fluoro-4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000212
3-[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]piperidin-1-yl]propanoic acid
Homo sapiens
-
-
0.00001
3-[1-[4-(benzothiazol-2-yloxy)benzyl]piperidin-4-yl]oxazolidin-2-one
Homo sapiens
-
-
0.01
3-[[4-(1-methylethyl)benzyl]sulfanyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-valine
Homo sapiens
-
IC50 above 0.01 mM
0.000003
4-([(1R,5S)-3-[(4-benzylphenyl)amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl)benzoic acid
Homo sapiens
-
-
0.000014
4-([(1R,5S)-3-[(4-phenoxyphenyl)amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl)benzoic acid
Homo sapiens
-
-
0.000007 - 0.0001
4-([2-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]pyrrolidin-1-yl]methyl)benzoic acid
0.000005
4-([4-[([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)methyl]piperidin-1-yl]methyl)benzoic acid
Homo sapiens
-
-
0.000015
4-([methyl[2-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)ethyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.00013
4-([methyl[2-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)ethyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.00033
4-([methyl[3-([2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.000003
4-([methyl[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)propyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.000009
4-([methyl[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)cyclohexyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.000007
4-([[2,2-dimethyl-3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl](methyl)amino]methyl)benzoic acid
Homo sapiens
-
-
0.000019
4-([[3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.00037
4-([[3-([2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)propyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.000011
4-([[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)cyclohexyl]amino]methyl)benzoic acid
Homo sapiens
-
-
0.000106
4-[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]piperidin-1-yl]butanoic acid
Homo sapiens
-
-
0.000049
4-[(2S)-2-([4-[4-(thiophen-3-yl)benzyl]phenoxy]methyl)piperidin-1-yl]butanoic acid
Homo sapiens
-
-
0.000053
4-[(2S)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]piperidin-1-yl]butanoic acid
Homo sapiens
-
-
0.00007
4-[(4-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]-1,4-diazepan-1-yl)methyl]benzoic acid
Homo sapiens
-
-
0.001
4-[(4-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperazin-1-yl)methyl]benzoic acid
Homo sapiens
-
-
0.000044
4-[(5-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]benzoic acid
Homo sapiens
-
-
0.000015
4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]-3-nitrobenzoic acid
Homo sapiens
-
-
0.000006
4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000025
4-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]cyclohexanecarboxylic acid
Homo sapiens
-
-
0.000016
4-[(methyl[[(2R)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperidin-2-yl]methyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000026
4-[(methyl[[(2R)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]pyrrolidin-2-yl]methyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000017
4-[(methyl[[(2S)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperidin-2-yl]methyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000017
4-[(methyl[[(2S)-1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]pyrrolidin-2-yl]methyl]amino)methyl]benzoic acid
Homo sapiens
-
-
0.000003
4-[2-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)ethyl]benzoic acid
Homo sapiens
-
-
0.000001
4-[2-[(1R,5S)-3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]ethyl]benzoic acid
Homo sapiens
-
-
0.000002
4-[2-[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]ethyl]benzoic acid
Homo sapiens
-
-
0.000003
4-[2-[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]ethyl]benzoic acid
Homo sapiens
-
-
0.000005
4-[[(1R,5S)-3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000008
4-[[(1R,5S)-3-([4-[4-(1,3-thiazol-2-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000004
4-[[(1R,5S)-3-([4-[4-(1H-pyrrol-1-yl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000013
4-[[(1R,5S)-3-([4-[4-(trifluoromethyl)phenoxy]phenyl]amino)-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000009
4-[[(1R,5S)-3-[[4-(1,3-benzothiazol-2-yloxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00032
4-[[(1R,5S)-3-[[4-(2-chlorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000006
4-[[(1R,5S)-3-[[4-(2-fluorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000006
4-[[(1R,5S)-3-[[4-(4-chlorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00004
4-[[(1R,5S)-3-[[4-(4-fluorophenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000023
4-[[(1R,5S)-3-[[4-(4-methoxyphenoxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000047
4-[[(1R,5S)-3-[[4-(benzyloxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000005
4-[[(1R,5S)-3-[[4-(biphenyl-4-yloxy)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000075
4-[[(1R,5S)-3-[[4-(pyridin-4-ylmethyl)phenyl]amino]-8-azabicyclo[3.2.1]oct-8-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000019
4-[[(3-[[2-([4-[(2R)-2-hydroxy-2-phenylethoxy]phenyl]amino)-2-oxoethyl](methyl)amino]propyl)(methyl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.00012
4-[[(3R)-3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)pyrrolidin-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000057
4-[[(3S)-3-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)pyrrolidin-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00006
4-[[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000007
4-[[3-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)pyrrolidin-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00006
4-[[4-(1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]hydrazino)piperidin-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00016
4-[[4-(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)azepan-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.000015
4-[[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)azepan-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00003
4-[[4-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)piperidin-1-yl]methyl]benzoic acid
Homo sapiens
-
-
0.00014
4-[[methyl(1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]azepan-4-yl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.00049
4-[[methyl(1-[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]piperidin-4-yl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.000005
4-[[methyl(3-[methyl[2-([4-[4-(1,3-oxazol-2-yl)phenoxy]phenyl]amino)-2-oxoethyl]amino]propyl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.000016
4-[[[3-[(2-[[4-(2-fluorophenoxy)phenyl]amino]-2-oxoethyl)(methyl)amino]propyl](methyl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.000017
4-[[[3-[(2-[[4-(4-chlorophenoxy)phenyl]amino]-2-oxoethyl)(methyl)amino]propyl](methyl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.000006
4-[[[3-[(2-[[4-(4-fluorophenoxy)phenyl]amino]-2-oxoethyl)(methyl)amino]propyl](methyl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.000003
4-[[[3-[[2-[(4-benzylphenyl)amino]-2-oxoethyl](methyl)amino]propyl](methyl)amino]methyl]benzoic acid
Homo sapiens
-
-
0.000028
5-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]furan-2-carboxylic acid
Homo sapiens
-
-
0.00004
6-chloro-2-[4-(piperidin-1-ylmethyl)phenoxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000029
6-fluoro-2-[4-(piperidin-1-ylmethyl)phenoxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.000033
7-methyl-2-[4-(piperidin-1-ylmethyl)phenoxy][1,3]thiazolo[4,5-b]pyridine
Homo sapiens
-
pH and temperature not specified in the publication
0.00005
acetic acid (1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-ylcarbamoyl)methyl ester
Homo sapiens
-
-
0.000021
acetic acid [1-[4-(benzothiazol-2-yloxy)benzyl]piperidin-4-ylcarbamoyl]methyl ester
Homo sapiens
-
-
0.0158
methyl 3-(2-(5-(3-phenoxybenzyloxy)-1H-indol-3-yl)ethylamino)propanoate
Homo sapiens
-
in 10 mM sodium phosphate, pH 7.4, at 37°C
0.000035
N-(1-[2-[4-(benzothiazol-2-yloxy)phenyl]ethyl]piperidin-4-yl)acetamide
Homo sapiens
-
-
0.000026
N-(1-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0000037
N-(1-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]piperidin-4-yl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000004
N-(8-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenoxy]ethyl]-8-azabicyclo[3.2.1]oct-3-yl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0000003
N-(8-[2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl]-8-azabicyclo[3.2.1]oct-3-yl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0000073
N-[(3-endo)-8-[[6-(1,3-benzothiazol-2-yloxy)-1-benzofuran-3-yl]methyl]-8-azabicyclo[3.2.1]oct-3-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0000016
N-[(3-endo)-8-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-8-azabicyclo[3.2.1]oct-3-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000013
N-[1-[4-(1,3-benzothiazol-2-yloxy)benzyl]piperidin-4-yl]-2-hydroxyacetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000008
N-[1-[4-(benzothiazol-2-yloxy)benzyl]piperidin-4-yl]-2-hydroxyacetamide
Homo sapiens
-
-
0.000083
N-[8-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)benzyl]-8-azabicyclo[3.2.1]oct-3-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.000004
N2-methyl-N-(4-phenoxyphenyl)-N2-[4-(1H-tetrazol-5-yl)benzyl]glycinamide
Homo sapiens
-
-
0.00011
N2-methyl-N2-[3-[methyl(4-oxobutyl)amino]propyl]-N-(4-phenoxyphenyl)glycinamide
Homo sapiens
-
-
0.000018
N2-methyl-N2-[4-[methyl(4-oxobutyl)amino]butyl]-N-(4-phenoxyphenyl)glycinamide
Homo sapiens
-
-
0.00016
N2-[3-(dimethylamino)propyl]-N2-methyl-N-(4-phenoxyphenyl)glycinamide
Homo sapiens
-
-
0.00009
N2-[3-[benzyl(methyl)amino]propyl]-N2-methyl-N-(4-phenoxyphenyl)glycinamide
Homo sapiens
-
-
0.000033
N2-[4-[(aminooxy)sulfinyl]benzyl]-N2-methyl-N-(4-phenoxyphenyl)glycinamide
Homo sapiens
-
-
0.000079
S-(4-cyclohexylbenzyl)-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.000024
S-(4-tert-butylbenzyl)-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.00021
S-[(4-cyclohexylphenyl)(phenyl)methyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.000055
S-[1-(4-cyclohexylphenyl)-1-methylethyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.000079
S-[1-methyl-1-[4-(1-methylethyl)phenyl]ethyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.00018
S-[1-[4-(1-methylethyl)phenyl]butyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.000055
S-[1-[4-(1-methylethyl)phenyl]ethyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.00051
S-[1-[4-(1-methylethyl)phenyl]pentyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.000067
S-[1-[4-(1-methylethyl)phenyl]propyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.00052
S-[2-methyl-1-[4-(1-methylethyl)phenyl]propyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.0009
S-[4-(diethylamino)benzyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.000091
S-[[4-(1-methylethyl)phenyl](phenyl)methyl]-N-[(2S)-2-methyl-3-sulfanylpropanoyl]-L-cysteine
Homo sapiens
-
-
0.00088
[(2R)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]piperidin-1-yl]acetic acid
Homo sapiens
-
-
0.0000073
1-(5-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000062
1-(5-[[6-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.00034
1-(5-[[6-([1,3]thiazolo[4,5-c]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.00237
1-(5-[[6-([1,3]thiazolo[4,5-c]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.0003
1-(5-[[6-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.00213
1-(5-[[6-([1,3]thiazolo[5,4-b]pyridin-2-yloxy)-1-benzofuran-3-yl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl)ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.000007
4-([2-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]pyrrolidin-1-yl]methyl)benzoic acid
Homo sapiens
-
-
0.0001
4-([2-[(methyl[2-oxo-2-[(4-phenoxyphenyl)amino]ethyl]amino)methyl]pyrrolidin-1-yl]methyl)benzoic acid
Homo sapiens
-
-
0.0024
methyl 3-(2-(5-(4-phenylbenzyloxy)-1H-indol-3-yl)ethylamino)propanoate
Homo sapiens
-
in 10 mM sodium phosphate, pH 7.4, at 37°C
0.0076
methyl 3-(2-(5-(4-phenylbenzyloxy)-1H-indol-3-yl)ethylamino)propanoate
Homo sapiens
-
in 10 mM sodium phosphate, pH 7.4, at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.1
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
human esophageal adenocarcinoma cell (EAC) and adjacent nontumor esophageal tissues reveal overexpression of LTA4H in EAC tissues compared to that in nontumor samples
LTA4H and BLT1 are highly expressed in colitis and correlate with colon adenocarcinoma
roughly two-thirds of the eosinophil population express 5-lipoxygenase (5-LO), and of those 5-LO-expressing cells, over 99% express both LTA4 hydrolase and LTC4 synthase. Peripheral blood eosinophils cultured in vitro produce LTB4 when unstimulated, and they release significantly elevated levels of LTB4 when stimulated with aspirin-lysine, PMA, and platelet-activating factor
upregulation of LTA4H expression in primary effusion lymphoma, which is a rare HIV-associated non-Hodgkin B cell lymphoma
additional information
LTA4H and BLT1 are overexpressed in colitis and correlate with colon adenocarcinoma, phenotypes, overview
additional information
LTA4H is overexpressed in several other human cancers, particularly lung adenocarcinoma, adenosquamous carcinoma, bronchioalveolar carcinoma, large cell carcinoma, thyroid adenocarcinoma, and gall bladder adenocarcinoma
additional information
-
enzyme is higher in columnar-lined esophagus, dysplastic, and total esophageal adenocarcinoma tissues than in basal cells of esophageal epithelium, however enzyme is expressed in the parabasal cells of esophageal squamous epithelium, enzyme is also overexpressed in other cancers, including colon and lung cancers
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
the short- and long-form mRNA expression levels of selected number of cell types is analysed by quantitative RT-PCR
-
additional information
-
the short- and long-form mRNA expression levels of selected number of cell types is analysed by quantitative RT-PCR
-
additional information
-
association with the plasma membrane during restricted infection with HIV-1
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
metabolism
physiological function
additional information
malfunction
leukotriene A4 hydrolase (LTA4H) regulates the balance between the anti-inflammatory lipoxins and pro-inflammatory leukotriene B4, with direct implications in tuberculosis-driven inflammation. In humans, a single nucleotide polymorphism in the LTA4H promoter which regulates its transcriptional activity (rs17525495) is identified and described to impact clinical severity of tuberculosis presentation and response to corticosteroid therapy. A higher incidence of severe tuberculosis-associated immune reconstitution inflammatorysyndrome among patients with mutant LTA4H genotypes is observed compared to the wild type, despite similar incidence of tuberculosis-associated immune reconstitution inflammatory syndrome and similar immune restoration in both groups. Steroids are effective in alleviating IRIS in all the genotypes
malfunction
imbalances in leukotriene B4 synthesis are related to several pathologic conditions
malfunction
inhibition of the LTB4 conversion ameliorates inflammation and leads to accumulation of pro-resolving Lipoxin A4 (LXA4) while inhibition of PGP degradation potentiates neutrophilic inflammation
malfunction
knocking out LTA4H significantly reduces skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model. LTA4H depletion dramatically decreases anchorage-dependent and -independent skin cancer cell growth by inducing cell cycle arrest at the G0/G1 phase. Depletion of LTA4H enhances p27 protein stability, which is associated with decreased phosphorylation of CDK2 at Thr160 and inhibition of the CDK2/cyclin E complex, resulting in down-regulated p27 ubiquitination. Cell phenotypes, overview
malfunction
LTB4 levels are persistently elevated in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide (LPS)-induced ALI, and the leukotriene levels in pulmonary edema fluid are significantly higher in ALI patients compared to control patients with hydrostatic pulmonary edema. In addition, LTB4 level is increased in lung homogenates, and BALF of patients with IPF and the level of LTB4 correlate with the extent of fibrosis in histological sections
malfunction
silencing of LTA4H translation by shRNA in HCT116 human colorectal carcinoma cells suppresses cell growth, stimulation of the aminopeptidase (AP) activity of LTA4H enhanced colony formation in HCT116 cells, indicating that LTA4H activity is associated with the malignant potential of CRC cells
metabolism
LTA4H is a key enzyme in the leukotriene pathway, which catalyzes the final and rate-determining step in the synthesis of LTB4
metabolism
leukotriene A4 hydrolase participates in the metabolism of lipid mediators and peptides
metabolism
the enzyme catalyzes the final rate-limiting step in the biosynthesis of leukotriene B4
metabolism
the enzyme is involved in the LTA4H/LTB4 biosynthesis pathway, overview. 5-Lipoxygenase catalyzes the conversion of to (5S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic (5-HpETE) to LTA4 in the presence of 5-lipoxygenase-activating protein (FLAP). LTA4 is unstable and hydrolyzes to LTB4 by LTA4H. LTB4 then activates the G protein-coupled receptors BLT1 and BLT2. Biosynthesis of LTB4 typically occurs in a cell that expresses both 5-LOX and LTA4H. LTA4H is expressed in cells and tissues without 5-LOX activity, indicating that they cannot produce the substrate for LTA4H, such as in erythrocytes and endothelial cells. LTB4 biosynthesis pathway and cancer development, overview
physiological function
leukotriene A4 hydrolase (LTA4H) regulates the balance between the anti-inflammatory lipoxins and pro-inflammatory leukotriene B4, with direct implications in tuberculosis-driven inflammation. In humans, a single nucleotide polymorphism in the LTA4H promoter which regulates its transcriptional activity (rs17525495) is identified and described to impact clinical severity of tuberculosis presentation and response to corticosteroid therapy. A higher incidence of severe tuberculosis-associated immune reconstitution inflammatorysyndrome among patients with mutant LTA4H genotypes is observed compared to the wild type, despite similar incidence of tuberculosis-associated immune reconstitution inflammatory syndrome and similar immune restoration in both groups. Steroids are effective in alleviating IRIS in all the genotypes
physiological function
ELR1 CXC chemokines (e.g. interleukin-8) bind to CXCR1 and CXCR2 receptors expressed on neutrophils, and attract them to sites of inflammation. Ensuing degradation of collagen by neutrophil-derived proteases generates many tripeptide proline-glycine-proline (PGP) peptides that mimic key sequences found in ELR1 CXC chemokines, and act as a potent neutrophil chemoattractant. Extracellular leukotriene (LT) A4 hydrolase (LTA4H) degrades PGP and resolves neutrophilic inflammation, whereas intracellular epoxide hydrolase function (EC 3.3.2.10) of the same enzyme converts LTA4 to LTB4. LTB4 is a proinflammatory lipid mediator capable of recruiting and activating an array of cells, including neutrophils. The intracellular activity of LTA4H within leukocytes can generate the lipid mediator LTB4 that can also promote neutrophil recruitment by binding to LTB4 receptor (BLT1).Thus, LTA4H exhibits opposing pro- and anti-inflammatory roles that govern neutrophil recruitment. Cigarette smoke disrupts leukotriene (LT) A4 hydrolase (LTA4H)-mediated resolution of pulmonary neutrophilic inflammation. In response to infection or injury, resident cells within the lung will release chemoattractants that will promote neutrophil recruitment from the vasculature and into the tissue. Epithelial cells and alveolar macrophages, for example, may release IL-8 that will bind to CXCR1/2 on the surface of the neutrophil and promote recruitment. Cigarette smoke chemically acetylates PGP, enhancing its chemotactic activity and protecting it from degradation by LTA4H. Second, biochemical and preliminary murine studies suggest that cigarette smoke can selectively abrogate the peptidase activity of LTA4H, with minimal effect on the hydrolase activity. Thus, cigarette smoke pushes LTA4H toward a uniquely proinflammatory phenotype, whereby LTB4 and PGP together induce increased pulmonary neutrophilic inflammation. Acrolein in cigarette smoke in part inhibits LTA4H peptidase activity. Acrolein, derived from cigarette smoke or physiologically during inflammation (lipid peroxidation, metabolism of threonine or spermine), can inhibit LTA4H-mediated degradation of PGP, allowing the peptide to accumulate and maintain neutrophilic inflammation. LTA4H enzyme inhibitors may fail to distinguish between the opposing activities of the enzyme, and could inadvertently lead to persistent neutrophilia
physiological function
enzyme leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme with epoxide hydrolase (EH) and aminopeptidase (AP) activities
physiological function
enzyme leukotriene A4 hydrolase (LTA4H) is characterized as a bifunctional enzyme with epoxide hydrolase (EH) and aminopeptidase (AP) activities. LTA4H plays a critical role in modulating inflammation by producing LTB4 via its EH activity. LTA4H also has putative roles in cancer development. An increased level of leukotriene B4 (LTB4), which is biosynthesized by leukotriene A4 hydrolase (LTA4H), is implicated in several types of cancer, including colon and prostate cancer. LTB4 is formed from an unstable intermediate, leukotriene A4 (LTA4). The aminopeptidase activity substrate proline-glycine-proline (PGP) generated from collagen acts as a proinflammatory factor by neutrophilic chemotaxis. Enzyme LTA4H precisely controls EH activity toward LTB4 and AP activity toward PGP
physiological function
in the eicosanoid metabolic processes, leukotriene A4 hydrolase (LTA4H) is an epoxide hydrolase that catalyzes conversion of the unstable allelic epoxide leukotriene A4 (LTA4) to leukotriene B4 (LTB4), which is known to have classical biological functions including chemotaxis, endothelial adherence, and activation of leukocytes. It exerts its actions through a transmembrane protein receptor, LTB4 receptor type 1 (BLT1). The leukotriene A4 hydrolase (LTA4H) pathway plays a role in colorectal cancer (CRC). High expression of LTA4H and leukotriene B4 receptor type 1 (BLT1) are also associated with CRC survival probability. High expression of LTA4H and BLT1 negatively correlate with CRC patient survival probability
physiological function
leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme that exhibits LTA4H and aminopeptidase activities, it is a key enzyme in the biosynthesis of leukotriene B4 (LTB4). LTA4H is well-known to regulate chemotactic activity of human neutrophils. LTB4 is secreted by neutrophils at inflammation sites in response to formyl peptides, playing an important role in neutrophil activation and migration to formyl peptides
physiological function
leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc metalloenzyme overexpressed in several human cancers. LTA4H regulates cell cycle and skin carcinogenesis. LTA4H is a key modulator of cell cycle through its negative effect on p27 expression. LTA4H mediates the G0/G1 cell cycle phase through p27 proteasome degradation and is is implicated in cell growth, cell cycle distribution. LTA4H mediates p27 stability through LTB4/BLT1 pathway. LTA4H and BLT1 influence the formation of the CDK2/cyclin E complex and the phosphorylation of CDK2 at Thr160
physiological function
leukotriene A4 hydrolase is a soluble enzyme with epoxide hydrolase and aminopeptidase activities catalysing the conversion of leukotriene A4 to leukotriene B4 and the hydrolysis of the peptide proline-glycine-proline. Bifunctional LTA4H shows two catalytic activities, aminopeptidase activity hydrolysing the tripeptide proline-glycine-proline (PGP), and epoxide hydrolase activity on leukotriene A4 (LTA4) generating leukotriene B4 (LTB4), a potent inducer of macrophage, T-lymphocyte and neutrophil chemotaxis
physiological function
the human leukotriene A4 hydrolase (LTA4H) is a 69 kDa protein involved in the arachidonic acid cascade. LTA4H converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4).1 LTB4 triggers the adhesion and aggregation of leukocytes in the endothelium2 and acts as an attractant for different leukocytes (monocytes, neutrophils, macrophages, and dendritic cells). The overproduction of LTB4 has been associated with different pathological conditions and diseases. The leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme, containing a peptidase and a hydrolase activity both activities having opposing functions regulating inflammatory response. The hydrolase activity is responsible for the conversion of leukotriene A4 to pro-inflammatory leukotriene B4
malfunction
-
the enzyme is linked to inflammation diseases, especially asthma and also rheumatoid arthritis, significant role for LTB4 production in the pathogenesis of asthma, overview. LTB4 and BLT1 may be involved in the steroid resistance experienced by some patients with asthma
metabolism
-
leukotriene A4 hydrolase catalyzes the final step in the synthesis of leukotriene B4, LTB4, a potent chemoattractant and proinflammatory eicosanoid
metabolism
-
leukotriene A4 hydrolase is a key enzyme in the leukotriene pathway, which hydrolyzes leukotriene A4 to leukotriene B4, a proinflammatory mediator
metabolism
-
LTA4H catalyzes the last step in the synthesis of the pro-inflammatory molecule leukotriene B4
metabolism
-
no difference in LTA4 hydrolase expression in patients with naturally occurring allergic rhinitis compared to controls, suggesting that LTB4 is less important chronically or that LTA4 hydrolase is not the rate-limiting step in its synthesis
physiological function
-
leukotrienes are involved in antiinflammation via eicosanoids, lipid mediators derived from arachidonic acid including the proinflammatory leukotrienes as well as the anti-inflammatory lipoxins, complex interplay between proinflammatory leukotrienes and antiinflammatory lipoxins. The enzyme is important in the balance between proinflammatory and anti-inflammatory responses in tuberculosis
additional information
binding pocket of the apo LTA4H protein (PDB entry 5FWQ) with bound Zn2+, overview
additional information
enzyme residues E271, D375, Arg563, and Lys555 are involved in enzyme-substrate interactions
additional information
-
enzyme residues E271, D375, Arg563, and Lys555 are involved in enzyme-substrate interactions
additional information
eosinophils express LTA4 hydrolase and release LTB4. In addition to neutrophils, epithelial cells, and certain phagocytes, eosinophils are classified as contributors to the generation of the inflammatory mediator LTB4. Leukotriene B4 (LTB4) is a potent neutrophil chemoattractant, and this mediator might be an alternative to the Th17 axis as a potential mechanism leading to airway neutrophils. The enzyme might play a role in asthma
additional information
LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein
additional information
-
LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein
additional information
the enzyme has two catalytic pockets, a hydrophobic domain that recognizes the lipophilic hydrocarbon chain of LTA4 and a hydrophilic domain that recognizes the N-terminal region of PGP. Both domains converge in a common catalytic zone where the carboxylate group of each substrate interacts with alkaline amino acids in the protein. Thus, different catalytic pockets for separate activities share a carboxylate group recognition zone
additional information
-
HIV-1 transforms the monocyte plasma membrane proteome including also cytosolic LTA4H, the process is linked to cell viability, overview
additional information
-
protection from both tuberculosis and multibacillary leprosy is associated with heterozygosity for LTA4H polymorphisms
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). LKHA4_HUMAN
611
0
69285
Swiss-Prot
other Location (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
69000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
additional information
LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein
additional information
-
LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with inhibitors SAHA or M344, X-ray diffraction structure determination and analysis
in complex with inhibitor N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine, to 1.9 A resolution, space group P212121. The inhibitor binds along the sequence signature for M1 aminopeptidases, GXMEN. It exhibits bidentate chelation of the catalytic zinc and binds to LTA4H's enzymatically essential carboxylate recognition site. The inhibitor binds in an extended beta-sheet conformation between the zinc ion and Arg563. The carboxyl moiety forms two hydrogen bonds with Arg563, and the hydroxamate moiety chelates the zinc ion in a bidentate fashion
liquid-liquid diffusion method, with 28% (w/v) polyethylene glycol, 100 mM imidazole pH 7.2, and 5 mM YbCl3
mutant E296Q in complex with N-(4-oxo-4-pyrrolidinyl-butanoyl)-L-proline, liquid/liquid diffusion method, using 22-30% (w/v) PEG 8000, 100 mM NaAc, 100 mM imidazole buffer (pH 6.5-7.0), and 5 mM YbCl3
mutant enzyme E296Q in complex with inhibitors RB3040 and RB3041, and substrate, liquid-liquid diffusion method, using 28% (w/v) polyethylene glycol, 50 mM Na acetate, 100 mM imidazole (pH 6.8), and 5 mM YbCl3
crystal structure of enzyme in complex with captopril, thioamine or hydroxamic acid
-
molecular docking studies with inhibitors. Position and size of substituted groups plays a key role in the binding conformation of the compounds. Compounds without branches, and p-substituted compounds tend to bind LTA4H in the channel, forming a hydrogen bond between the pyrrolidine nitrogen atom and Gly269 main-chain oxygen atom. o- or m-Substituted compounds can stay at the entrance part of the pocket in a reversed orientation with three hydrogen bonds, the nitrogen atom to Gln136, the oxygen atom connected to alkyl group to His295, and the oxygen atom connected to bibenzyl to Gly268 main-chain nitrogen atom
-
the structure of LTA4H in complex with the competitive inhibitor is determined
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D368N
epoxide hydrolase activity: 72% of Km of wild type enzyme, aminopeptidase activity: 107% of Km of wild type enzyme
D371N
epoxide hydrolase activity: 51% of Km of wild type enzyme, aminopeptidase activity: 77% of Km of wild type enzyme
D373N
epoxide hydrolase activity: 43% of Km of wild type enzyme, aminopeptidase activity: 101% of Km of wild type enzyme
D375A
D375E
complete loss of the epoxide hydrolase activity, aminopeptidase activity: 152% of Km of wild type enzyme
D375N
complete loss of the epoxide hydrolase activity, aminopeptidase activity exhibits unsaturable enzyme kinetic
E296Q
H139Q
epoxide hydrolase activity: 167% of Km of wild type enzyme, aminopeptidase activity: 359% of Km of wild type enzyme
Q134A
epoxide hydrolase activity exhibits unsaturable enzyme kinetics within the range observed, aminopeptidase activity: 157% of Km of wild type enzyme
Q134L
significantly increased epoxide hydrolase activity, aminopeptidase activity: 87% of Km of wild type enzyme
Q134N
epoxide hydrolase activity: 148% of Km of wild type enzyme, aminopeptidase activity: 108% of Km of wild type enzyme
Y267F
epoxide hydrolase activity: 58% of Km of wild type enzyme, aminopeptidase activity: 64% of Km of wild type enzyme
E271Q
E297A
-
30% hydrolase activity, 25% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
E297D
-
17% hydrolase activity, 38% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
E297K
-
13% hydrolase activity, 16% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
E297Q
-
104% hydrolase activity, 14% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
E318A
-
the exposure of mutant enzyme to leukotriene A4, leukotriene methyl ester or leukotriene ethyl ester results in covalent modification of peptide K21 to the same extent as for wild-type enzyme
E319K
-
0% hydrolase activity, 12% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
G268A
-
epoxide hydrolase activity: 97% of Km of wild type enzyme, aminopeptidase activity: 73% of Km of wild type enzyme
G269A
-
epoxide hydrolase activity: 202% of Km of wild type enzyme, aminopeptidase activity: 66% of Km of wild type enzyme
M270L
-
epoxide hydrolase activity: 21% of Km of wild type enzyme, aminopeptidase activity: 189% of Km of wild type enzyme
N272A
-
epoxide hydrolase activity: 30% of Km of wild type enzyme, aminopeptidase activity: 221% of Km of wild type enzyme
Q136A
-
epoxide hydrolase activity: 67% of Km of wild type enzyme, aminopeptidase activity: 108% of Km of wild type enzyme
Q136N
-
epoxide hydrolase activity: 18% of Km of wild type enzyme, aminopeptidase activity: 24% of Km of wild type enzyme
S379A
-
26% hydrolase activity, 4% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
S380A
-
54% hydrolase activity, 68% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
S415D
-
significantly reduced epoxide hydrolase activity, little effect on aminopeptidase activity
S415E
-
significantly reduced epoxide hydrolase activity, little effect on aminopeptidase activity
Y378F
Y378Q
Y384F
-
0% hydrolase activity, 13% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
additional information
D375A
near-complete loss of the epoxide hydrolase activity, aminopeptidase activity exhibits unsaturable enzyme kinetic
Y378F
-
173% hydrolase activity, 43% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme, mutant enzyme is resistant to suicide inactivation
Y378F
-
products are leukotriene B4 and 5S,12R-dihydroxy-6,10-trans-8,14-cis-eicosatetraenic acid, 203% hydrolase activity, 81% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
Y378F
-
mutant is only partially protected against inactivation by leukotriene methyl ester and leukotriene ethyl ester
Y378Q
-
mutant is only partially protected against inactivation by leukotriene methyl ester and leukotriene ethyl ester
Y378Q
-
34% hydrolase activity, 1.6% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme, mutant enzyme is resistant to suicide inactivation
Y378Q
-
products are leukotriene B4 and 5S,12R-dihydroxy-6,10-trans-8,14-cis-eicosatetraenic acid, 45% hydrolase activity, 3% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme
additional information
mutations of residues Glu271 and Glu296, as well as Asp375 are critical for LTA4H enzymatic activity
additional information
-
a single-nucleotide polymorphism and a particular haplotype for the LTA4H gene are linked to an increased risk for the development of asthma, overview
additional information
-
mutations in the leukotriene A4 hydrolase gene result in decreased lta4h mRNA expression and increased susceptibility to Mycobacterial infection. lta4h mutations confer hypersusceptibility independent of LTB4 reduction, by redirecting eicosanoid substrates to anti-inflammatory lipoxins. The resultant anti-inflammatory state permits increased mycobacterial proliferation by limiting production of tumor necrosis factor. Lta4h deficiencies result in an immunoregulatory phenotype, overview. Two single-nucleotide polymorphisms are rs1978331 and rs2660898, overview
additional information
-
positive correlation between LTA4H polymorphism and the amount of LTB4 produced in vitro by granulocytes from the affected individuals. Heterozygosity at LTA4H is also associated with increased LTB4 production in vivo resulting in enhanced protection from TB or leprosy
additional information
-
two single-nucleotide polymorphisms within the LTA4H gene, rs17525488 and rs2540493, are protective against asthma in individuals from Mexico and Puerto Rico. Among the Mexican patients, LTA4H polymorphisms are associated with baseline lung function and IgE levels. Identification of a gene-gene interaction between LTA4H, rs17525488, and arachidonate 5-lipoxygenase-activating protein gene ALOX5AP, rs1050739
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
enzyme is unstable in aqueous buffer solutions at pH 7.8 and 25°C and nonenzymatically hydrolysed, half-life less than 10 s
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged enzyme by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli JM101 cells
identification of two isoforms of the mRNA, short and long, by using a sequential reverse transcriptase (RT)-PCR mapping approach, both enzyme mRNAs are expressed in blood cells, endothelial cells, smooth muscle cells, fibroblasts and tumor cells
recombinant expression of human LTA4H with C-terminal hexahistidine tag and N-terminal T7 gene leader sequence
high-level expression enzyme in Spodoptera frugiperda cells infected with baculovirus vector
-
the enzyme is encoded in the lta4h locus, lta4h interacts with the TNF signaling pathway. LthA4 genotyping in leprosy patients from Vietnam and Nepal, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
human esophageal adenocarcinoma cell (EAC) and adjacent nontumor esophageal tissues reveal overexpression of LTA4H in EAC tissues compared to that in nontumor samples. LTA4H is overexpressed in several other human cancers, particularly lung adenocarcinoma, adenosquamous carcinoma, bronchioalveolar carcinoma, large cell carcinoma, thyroid adenocarcinoma, and gall bladder adenocarcinoma. Upregulation of LTA4H expression in primary effusion lymphoma, which is a rare HIV-associated non-Hodgkin B cell lymphoma
knockdown of LTA4H inhibits anchorage-independent growth of HCT116 colon cancer cells
the enzyme is induced by HIV-1 infection, facilitating the protein transformation from the cytosol to the plasma membrane, which is linked to cathepsin B- and caspase 9, 3-dependent apoptosis, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
LTB4 can serve as a biomarker for evaluating bestatin efficacy in colorectal cancer and the antitumor effects of bestatin through its targeting of LTA4H
drug development
medicine
pharmacology
leukotriene 4 hydrolase is a key target for the treatment of cardiovascular disease
diagnostics
-
LTA4H genes are risk factors for asthma in two different ethnic groups, individuals from Mexico and Puerto Rico
medicine
drug development
development of LTA4H inhibitors in cancer prevention and therapy
drug development
drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis. Inhibiting LTB4 biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF)
drug development
possible therapeutic potential of targeting LTB4/BLT signaling in asthma, but production of LTB4 may not be responsible for airway neutrophils in severe asthma
drug development
the bifunctional enzyme is a target for development of selective inhibitors
medicine
the enzyme catalyses the hydrolysis of leukotriene A4 into the proinflammatory substance leukotriene B4
medicine
-
the enzyme catalyses the hydrolysis of leukotriene A4 into the proinflammatory substance leukotriene B4
medicine
findings suggest that agents affecting LTB4 biosynthetic pathway may prove useful for primary or secondary prevention of heart attacks
medicine
LTB4 can serve as a biomarker for evaluating bestatin efficacy in colorectal cancer and the antitumor effects of bestatin through its targeting of LTA4H
medicine
-
the lipid metabolic activity of enzyme plays a central role in the control of polymorphonuclear leukocyte function and in the development of inflammation, the regulation of enzyme presents a novel potential target for anti-inflammatory therapy
medicine
-
enzyme overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of esophageal adenocarcinogenesis
medicine
-
the product is a classical chemoattractant, triggers adherence and aggregation of leukocytes to the endothelium, modulates immune responses, participates in the host-defence against infections and is a mediator of PAF-induced lethal shock
medicine
-
the enzyme catalyses the hydrolysis of leukotriene A4 into the proinflammatory substance leukotriene B4
medicine
-
LTA4H appears to be a promising target for development of drugs for prevention and treatment of atherosclerosis and its associated thrombotic complications
medicine
-
understanding the molecular alterations that influence primary effusion lymphoma development will aid in the identification of novel therapeutic targets, as well as potential risk factors for this desease
medicine
-
inhibition of LTB4 synthesis may be beneficial in the treatment of severe asthma and viral exacerbations of asthma, in which neutrophilic inflammation is more prominent
medicine
-
inhibition of this enzyme can be a valid method in the treatment of inflammatory response exhibited through leukotriene B4
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ohishi, N.; Izumi, T.; Seyama, Y.; Shimizu, T.
Purification and characterization of human lung leukotriene A4 hydrolase
Methods Enzymol.
187
286-295
1990
Homo sapiens
Samuelsson, B.; Funk, C.D.
Enzymes involved in the biosynthesis of leukotriene B4
J. Biol. Chem.
264
19469-19472
1989
Cavia porcellus, Homo sapiens, Rattus norvegicus
Bigby, T.D.; Lee, D.M.; Minami, M.; Ohishi, N.; Shimizu, T.; Baker, J.R.
Characterization of human airway epithelial cell leukotriene A4 hydrolase
Am. J. Respir. Cell Mol. Biol.
11
615-624
1994
Homo sapiens
Gierse, J.K.; Luckow, V.A.; Askonas, L.J.; Duffin, K.L.; Aykent, S.; Bild, G.S.; Rodi, C.P.; Sullivan, P.M.; Bourner, M.J.
High-level expression and purification of human leukotriene A4 hydrolase from insect cells infected with a baculovirus vector
Protein Expr. Purif.
4
358-366
1993
Homo sapiens
Radmark, O.; Shimizu, T.; Jrnvall, H.; Samuelsson, B.
Leukotriene A4 hydrolase in human leukocytes. Purification and properties
J. Biol. Chem.
259
12339-12345
1984
Homo sapiens
Haeggstrm, J.; Radmark, O.; Fitzpatrick, F.A.
Leukotriene A4-hydrolase activity in guinea pig and human liver
Biochim. Biophys. Acta
835
378-384
1985
Cavia porcellus, Homo sapiens
Haeggstrm, J.Z.; Wetterholm, A.; Shapiro, R.; Vallee, B.L.; Samuelsson, B.
Leukotriene A4 hydrolase: a zinc metalloenzyme
Biochem. Biophys. Res. Commun.
172
965-970
1990
Homo sapiens
Minami, M.; Ohishi, N.; Mutho, H.; Izumi, T.; Bito, H.; Wada, H.; Seyama, Y.; Toh, H.; Shimizu, T.
Leukotriene A4 hydrolase is a zinc-containing aminopeptidase
Biochem. Biophys. Res. Commun.
173
620-626
1990
Cavia porcellus, Homo sapiens
Haeggstrm, J.Z.; Wetterholm, A.; Vallee, B.L.; Samuelsson, B.
Leukotriene A4 hydrolase: an epoxide hydrolase with peptidase activity
Biochem. Biophys. Res. Commun.
173
431-437
1990
Homo sapiens
Nathaniel, D.J.; Evans, J.F.; Leblanc, Y.; Leveille, C.; Fitzsimmons, B.J.; Ford-Hutchinson, A.W.
Leukotriene A5 is a substrate and an inhibitor of rat and human neutrophil LTA4 hydrolase
Biochem. Biophys. Res. Commun.
131
827-835
1985
Homo sapiens, Rattus norvegicus
Ohishi, N.; Izumi, T.; Minami, M.; Kitamura, S.; Seyama, Y.; Ohkawa, S.; Terao, S.; Yotsumoto, H.; Takaku, F.; Shimizu, T.
Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers
J. Biol. Chem.
262
10200-10205
1987
Homo sapiens
Oring, L.; Krivi, G.; Fitzpatrick, F.A.
Leukotriene A4 hydrolase. Inhibition by bestatin and intrinsic aminopeptidase activity establish its functional resemblance to metallohydrolase enzymes
J. Biol. Chem.
266
1375-1378
1991
Homo sapiens
Wetterholm, A.; Haeggstrm, J.Z.
Leukotriene A4 hydrolase: an anion activated peptidase
Biochim. Biophys. Acta
1123
275-281
1992
Homo sapiens
Minami, M.; Bito, H.; Ohishi, N.; Tsuge, H.; Miyano, M.; Mori, M.; Wada, H.; Mutoh, H.; Shimada, S.; Izumi, T.; Abe, K.; Shimizu, T.
Leukotriene A4 hydrolase, a bifunctional enzyme. Distinction of leukotriene A4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297
FEBS Lett.
309
353-357
1992
Homo sapiens
Yuan, W.; Wong, C.H.; Haeggstrm, J.Z.; Wetterholm, A.; Samuelsson, B.
Novel tight-binding inhibitors of leukotriene A4 hydrolase
J. Am. Chem. Soc.
114
6552-6553
1992
Homo sapiens
-
Tsuge, H.; Ago, H.; Aoki, M.; Furuno, M.; Noma, M.; Miyano, M.
Crystallization and preliminary X-ray crystallographic studies of recombinant human leukotriene A4 hydrolase complexed with bestatin
J. Mol. Biol.
238
854-856
1994
Homo sapiens
Iversen, L.; Kristensen, P.; Nissen, J.B.; Merrick, W.C.; Kragballe, K.
Purification and characterization of leukotriene A4 hydrolase from human epidermis
FEBS Lett.
358
316-322
1995
Homo sapiens
Wetterholm, A.; Haeggstrom, J.Z.; Samuelsson, B.; Yuan, W.; Munoz, B.; Wong, C.H.
Potent and selective inhibitors of leukotriene A4 hydrolase: effects on purified enzyme and human polymorphonuclear leukocytes
J. Pharmacol. Exp. Ther.
275
31-37
1995
Homo sapiens
Wetterholm, A.; Macchia, L.; Haeggstroem, J.Z.
Metal inhibition of LTA4 hydrolase and cellular 5-lipoxygenase activity
Adv. Prostaglandin Thromboxane Leukot. Res.
23
179-181
1995
Homo sapiens
Mueller, M.J.; Samuelsson, B.; Haeggstrom, J.Z.
Chemical modification of leukotriene A4 hydrolase. Indications for essential tyrosyl and arginyl residues at the active site
Biochemistry
34
3536-3543
1995
Homo sapiens
Mueller, M.J.; Blomster, M.; Oppermann, U.C.; Jornvall, H.; Samuelsson, B.; Haeggstrom, J.Z.
Leukotriene A4 hydrolase: protection from mechanism-based inactivation by mutation of tyrosine-378
Proc. Natl. Acad. Sci. USA
93
5931-5935
1996
Homo sapiens
Mueller, M.J.; Andberg, M.B.; Samuelsson, B.; Haeggstrom, J.Z.
Leukotriene A4 hydrolase, mutation of tyrosine 378 allows conversion of leukotriene A4 into an isomer of leukotriene B4
J. Biol. Chem.
271
24345-24348
1996
Homo sapiens
Wetterholm, A.; Haeggstrom, J.Z.
Leukotriene A4 hydrolase: differential inhibition of the catalytic activities by divalent cations
Adv. Exp. Med. Biol.
400A
153-157
1997
Homo sapiens
Mueller, M.J.; Andberg, M.; Haeggstrom, J.Z.
Analysis of the molecular mechanism of substrate-mediated inactivation of leukotriene A4 hydrolase
J. Biol. Chem.
273
11570-11575
1998
Homo sapiens
Kull, F.; Ohlson, E.; Haeggstrom, J.Z.
Cloning and characterization of a bifunctional leukotriene A4 hydrolase from Saccharomyces cerevisiae
J. Biol. Chem.
274
34683-34690
1999
Caenorhabditis elegans, Homo sapiens, Saccharomyces cerevisiae
Stromberg-Kull, F.; Haeggstrom, J.Z.
Purification and characterization of leukotriene A4 hydrolase from Xenopus laevis oocytes
FEBS Lett.
433
219-222
1998
Homo sapiens, Xenopus laevis
Kull, F.; Ohlson, E.; Lind, B.; Haeggstrom, J.Z.
Saccharomyces cerevisiae leukotriene A4 hydrolase: formation of leukotriene B4 and identification of catalytic residues
Biochemistry
40
12695-12703
2001
Homo sapiens, Saccharomyces cerevisiae
Rudberg, P.C.; Tholander, F.; Thunnissen, M.M.; Haeggstrom, J.Z.
Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms
J. Biol. Chem.
277
1398-1404
2002
Homo sapiens
Rudberg, P.C.; Tholander, F.; Thunnissen, M.M.; Samuelsson, B.; Haeggstrom, J.Z.
Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375
Proc. Natl. Acad. Sci. USA
99
4215-4220
2002
Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens (P09960)
Andersson, B.; Kull, F.; Haeggstrom, J.Z.; Thunnissen, M.M.
Crystallization and X-ray diffraction data analysis of leukotriene A4 hydrolase from Saccharomyces cerevisiae
Acta Crystallogr. Sect. D
59
1093-1095
2003
Saccharomyces cerevisiae, Homo sapiens
Thunnissen, M.M.G.M.; Nordlund, P.; Haeggstrom, J.Z.
Crystal structure of human leukotriene A4 hydrolase, a bifunctional enzyme in inflammation
Nat. Struct. Biol.
8
131-135
2001
Homo sapiens (P09960), Homo sapiens
Haeggstrom, J.Z.; Kull, F.; Rudberg, P.C.; Tholander, F.; Thunnissen, M.M.
Leukotriene A4 hydrolase
Prostaglandins
68-69
495-510
2002
Saccharomyces cerevisiae, Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus, Xenopus laevis
Jendraschak, E.; Kaminski, W.E.; Kiefl, R.; von Schacky, C.
The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms
Biochem. J.
314
733-737
1996
Homo sapiens (P09960), Homo sapiens
Thunnissen, M.M.; Andersson, B.; Samuelsson, B.; Wong, C.H.; Haeggstrom, J.Z.
Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors
FASEB J.
16
1648-1650
2002
Homo sapiens
Menard, A.; Papini, E.; Mock, M.; Montecucco, C.
The cytotoxic activity of Bacillus anthracis lethal factor is inhibited by leukotriene A4 hydrolase and metallopeptidase inhibitors
Biochem. J.
320
687-691
1996
Homo sapiens
Chen, X.; Li, N.; Wang, S.; Wu, N.; Hong, J.; Jiao, X.; Krasna, M.J.; Beer, D.G.; Yang, C.S.
Leukotriene A4 hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin
J. Natl. Cancer Inst.
95
1053-1061
2003
Homo sapiens, Rattus norvegicus (P30349)
Rybina, I.V.; Feinmark, S.J.
Alteration of human leukotriene A4 hydrolase activity after site-directed mutagenesis: serine-415 is a regulatory residue
Biochim. Biophys. Acta
1438
199-203
1999
Homo sapiens
Orning, L.; Fitzpatrick, F.A.
Modification of leukotriene A4 hydrolase/aminopeptidase by sulfhydryl-blocking reagents: Differential effects on dual enzyme activities by methyl-methane thiosulfonate
Arch. Biochem. Biophys.
368
131-138
1999
Homo sapiens
Albrecht, S.; Defoin, A.; Salomon, E.; Tarnus, C.; Wetterholm, A.; Haeggstroem, J.Z.
Synthesis and structure activity relationships of novel non-peptidic metallo-aminopeptidase inhibitors
Bioorg. Med. Chem.
14
7241-7257
2006
Homo sapiens
Jame, A.J.; Lackie, P.M.; Cazaly, A.M.; Sayers, I.; Penrose, J.F.; Holgate, S.T.; Sampson, A.P.
Human bronchial epithelial cells express an active and inducible biosynthetic pathway for leukotrienes B4 and C4
Clin. Exp. Allergy
37
880-892
2007
Homo sapiens
Arguello, M.; Paz, S.; Hernandez, E.; Corriveau-Bourque, C.; Fawaz, L.M.; Hiscott, J.; Lin, R.
Leukotriene A4 hydrolase expression in PEL cells is regulated at the transcriptional level and leads to increased leukotriene B4 production
J. Immunol.
176
7051-7061
2006
Homo sapiens
Helgadottir, A.; Manolescu, A.; Helgason, A.; Thorleifsson, G.; Thorsteinsdottir, U.; Gudbjartsson, D.F.; Gretarsdottir, S.; Magnusson, K.P.; Gudmundsson, G.; Hicks, A.; Jonsson, T.; Grant, S.F.; Sainz, J.; OBrien, S.J.; Sveinbjornsdottir, S.; Valdimarsson, E.M.; Matthiasson, S.E.; Levey, A.I.; Abramson, J.L.; Reilly, M.P.; Vaccarino, V.; Wolfe, M.L.; Gudnason, V.; Quyyumi, A.A.; Topol, E.J.; Rader, D.J.; Thorgeirsson, G.; Gulcher, J.R.; Hakonarson, H.; Kong, A.; Stefansson, K.
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction
Nat. Genet.
38
68-74
2006
Homo sapiens (P09960)
Qiu, H.; Gabrielsen, A.; Agardh, H.E.; Wan, M.; Wetterholm, A.; Wong, C.H.; Hedin, U.; Swedenborg, J.; Hansson, G.K.; Samuelsson, B.; Paulsson-Berne, G.; Haeggstroem, J.Z.
Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability
Proc. Natl. Acad. Sci. USA
103
8161-8166
2006
Homo sapiens, Mus musculus
Haeggstroem, J.Z.; Tholander, F.; Wetterholm, A.
Structure and catalytic mechanisms of leukotriene A4 hydrolase
Prostaglandins Other Lipid Mediat.
83
198-202
2007
Homo sapiens
Ye, B.; Bauman, J.; Chen, M.; Davey, D.; Khim, S.K.; King, B.; Kirkland, T.; Kochanny, M.; Liang, A.; Lentz, D.; May, K.; Mendoza, L.; Phillips, G.; Selchau, V.; Schlyer, S.; Tseng, J.L.; Wei, R.G.; Ye, H.; Parkinson, J.; Guilford, W.J.
Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase
Bioorg. Med. Chem. Lett.
18
3891-3894
2008
Homo sapiens
Khim, S.K.; Bauman, J.; Evans, J.; Freeman, B.; King, B.; Kirkland, T.; Kochanny, M.; Lentz, D.; Liang, A.; Mendoza, L.; Phillips, G.; Tseng, J.L.; Wei, R.G.; Ye, H.; Yu, L.; Parkinson, J.; Guilford, W.J.
Discovery of novel and potent aryl diamines as leukotriene A4 hydrolase inhibitors
Bioorg. Med. Chem. Lett.
18
3895-3898
2008
Homo sapiens
Enomoto, H.; Morikawa, Y.; Miyake, Y.; Tsuji, F.; Mizuchi, M.; Suhara, H.; Fujimura, K.; Horiuchi, M.; Ban, M.
Synthesis and biological evaluation of N-mercaptoacylproline and N-mercaptoacylthiazolidine-4-carboxylic acid derivatives as leukotriene A4 hydrolase inhibitors
Bioorg. Med. Chem. Lett.
18
4529-4532
2008
Homo sapiens
Enomoto, H.; Morikawa, Y.; Miyake, Y.; Tsuji, F.; Mizuchi, M.; Suhara, H.; Fujimura, K.; Horiuchi, M.; Ban, M.
Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors
Bioorg. Med. Chem. Lett.
19
442-446
2009
Homo sapiens
Kirkland, T.A.; Adler, M.; Bauman, J.G.; Chen, M.; Haeggstroem, J.Z.; King, B.; Kochanny, M.J.; Liang, A.M.; Mendoza, L.; Phillips, G.B.; Thunnissen, M.; Trinh, L.; Whitlow, M.; Ye, B.; Ye, H.; Parkinson, J.; Guilford, W.J.
Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase
Bioorg. Med. Chem.
16
4963-4983
2008
Homo sapiens (P09960)
Tholander, F.; Muroya, A.; Roques, B.P.; Fournie-Zaluski, M.C.; Thunnissen, M.M.; Haeggstroem, J.Z.
Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design
Chem. Biol.
15
920-929
2008
Homo sapiens (P09960)
Houard, X.; Ollivier, V.; Louedec, L.; Michel, J.B.; Baeck, M.
Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophil-derived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombus
FASEB J.
23
1376-1383
2009
Homo sapiens
Crosslin, D.R.; Shah, S.H.; Nelson, S.C.; Haynes, C.S.; Connelly, J.J.; Gadson, S.; Goldschmidt-Clermont, P.J.; Vance, J.M.; Rose, J.; Granger, C.B.; Seo, D.; Gregory, S.G.; Kraus, W.E.; Hauser, E.R.
Genetic effects in the leukotriene biosynthesis pathway and association with atherosclerosis
Hum. Genet.
125
217-229
2009
Homo sapiens
Bauvois, C.; Jacquamet, L.; Huston, A.L.; Borel, F.; Feller, G.; Ferrer, J.L.
Crystal structure of the cold-active aminopeptidase from Colwellia psychrerythraea, a close structural homologue of the human bifunctional leukotriene A4 hydrolase
J. Biol. Chem.
283
23315-23325
2008
Homo sapiens (P09960), Homo sapiens
Grice, C.A.; Tays, K.L.; Savall, B.M.; Wei, J.; Butler, C.R.; Axe, F.U.; Bembenek, S.D.; Fourie, A.M.; Dunford, P.J.; Lundeen, K.; Coles, F.; Xue, X.; Riley, J.P.; Williams, K.N.; Karlsson, L.; Edwards, J.P.
Identification of a potent, selective, and orally active leukotriene A4 hydrolase inhibitor with anti-inflammatory activity
J. Med. Chem.
51
4150-4169
2008
Homo sapiens
Enache, L.A.; Zhang, J.; Sullins, D.W.; Kennedy, I.; Onua, E.; Zembower, D.E.; Muellner, F.W.; Singh, J.; Kiselyov, A.S.
Synthesis and structural assignment of two major metabolites of the LTA4H inhibitor DG-051
Bioorg. Med. Chem. Lett.
19
6275-6279
2009
Canis lupus familiaris, Homo sapiens, Rattus norvegicus
Sandanayaka, V.; Mamat, B.; Bhagat, N.; Bedell, L.; Halldorsdottir, G.; Sigthorsdottir, H.; Andresson, T.; Kiselyov, A.; Gurney, M.; Singh, J.
Discovery of novel leukotriene A4 inhibitors based on piperidine and piperazine scaffolds
Bioorg. Med. Chem. Lett.
20
2851-2854
2010
Homo sapiens
Jeong, C.H.; Bode, A.M.; Pugliese, A.; Cho, Y.Y.; Kim, H.G.; Shim, J.H.; Jeon, Y.J.; Li, H.; Jiang, H.; Dong, Z.
[6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase
Cancer Res.
69
5584-5591
2009
Mus musculus, Homo sapiens (P09960)
Scanga, C.A.; Flynn, J.L.
Mycobacterial infections and the inflammatory seesaw
Cell Host Microbe
7
177-179
2010
Homo sapiens
Kadiu, I.; Wang, T.; Schlautman, J.D.; Dubrovsky, L.; Ciborowski, P.; Bukrinsky, M.; Gendelman, H.E.
HIV-1 transforms the monocyte plasma membrane proteome
Cell. Immunol.
258
44-58
2009
Homo sapiens
Tobin, D.M.; Vary, J.C.; Ray, J.P.; Walsh, G.S.; Dunstan, S.J.; Bang, N.D.; Hagge, D.A.; Khadge, S.; King, M.C.; Hawn, T.R.; Moens, C.B.; Ramakrishnan, L.
The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans
Cell
140
717-730
2010
Danio rerio, Homo sapiens
Westergren, V.S.; Wilson, S.J.; Penrose, J.F.; Howarth, P.H.; Sampson, A.P.
Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis
Clin. Exp. Allergy
39
820-828
2009
Homo sapiens
Via, M.; De Giacomo, A.; Corvol, H.; Eng, C.; Seibold, M.A.; Gillett, C.; Galanter, J.; Sen, S.; Tcheurekdjian, H.; Chapela, R.; Rodriguez-Santana, J.R.; Rodriguez-Cintron, W.; Thyne, S.; Avila, P.C.; Choudhry, S.; Gonzalez Burchard, E.; Gonzalez Burchard, E.
The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos
Clin. Exp. Allergy
40
582-589
2010
Homo sapiens
Fourie, A.M.
Modulation of inflammatory disease by inhibitors of leukotriene A4 hydrolase
Curr. Opin. Investig. Drugs
10
1173-1182
2009
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Davies, D.R.; Mamat, B.; Magnusson, O.T.; Christensen, J.; Haraldsson, M.H.; Mishra, R.; Pease, B.; Hansen, E.; Singh, J.; Zembower, D.; Kim, H.; Kiselyov, A.S.; Burgin, A.B.; Gurney, M.E.; Stewart, L.J.
Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography
J. Med. Chem.
52
4694-4715
2009
Homo sapiens (P09960)
Sandanayaka, V.; Mamat, B.; Mishra, R.K.; Winger, J.; Krohn, M.; Zhou, L.M.; Keyvan, M.; Enache, L.; Sullins, D.; Onua, E.; Zhang, J.; Halldorsdottir, G.; Sigthorsdottir, H.; Thorlaksdottir, A.; Sigthorsson, G.; Thorsteinnsdottir, M.; Davies, D.R.; Stewart, L.J.; Zembower, D.E.; Andresson, T.; Kise, K.i.s.e.l.
Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis
J. Med. Chem.
53
573-585
2010
Homo sapiens (P09960), Homo sapiens
Tholander, F.; Roques, B.P.; Fournie-Zaluski, M.C.; Thunnissen, M.M.; Haeggstroem, J.Z.
Crystal structure of leukotriene A4 hydrolase in complex with kelatorphan, implications for design of zinc metallopeptidase inhibitors
FEBS Lett.
584
3446-3451
2010
Homo sapiens (P09960)
Thangapandian, S.; John, S.; Sakkiah, S.; Lee, K.W.
Molecular docking and pharmacophore filtering in the discovery of dual-inhibitors for human leukotriene A4 hydrolase and leukotriene C4 synthase
J. Chem. Inf. Model.
51
33-44
2011
Homo sapiens
Chen, Z.; Wu, Y.; Liu, Y.; Yang, S.; Chen, Y.; Lai, L.
Discovery of dual target inhibitors against cyclooxygenases and leukotriene A4 hydrolyase
J. Med. Chem.
54
3650-3660
2011
Homo sapiens
Snelgrove, R.; Kheradmand, F.; DeBakey, M.
Leukotriene A4 hydrolase: The janus enzyme shows its ugly side in smokers
Am. J. Respir. Crit. Care Med.
190
5-7
2014
Homo sapiens
Byzia, A.; Haeggstroem, J.Z.; Salvesen, G.S.; Drag, M.
A remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural amino acids
Amino Acids
46
1313-1320
2014
Homo sapiens
Tanis, V.M.; Bacani, G.M.; Blevitt, J.M.; Chrovian, C.C.; Crawford, S.; De Leon, A.; Fourie, A.M.; Gomez, L.; Grice, C.A.; Herman, K.; Kearney, A.M.; Landry-Bayle, A.M.; Lee-Dutra, A.; Nelson, J.; Riley, J.P.; Santillan, A.; Wiener, J.J.; Xue, X.; Young, A.L.
Azabenzthiazole inhibitors of leukotriene A4 hydrolase
Bioorg. Med. Chem. Lett.
22
7504-7511
2012
Homo sapiens
Eccles, W.; Blevitt, J.M.; Booker, J.N.; Chrovian, C.C.; Crawford, S.; de Leon, A.R.; Deng, X.; Fourie, A.M.; Grice, C.A.; Herman, K.; Karlsson, L.; Kearney, A.M.; Lee-Dutra, A.; Liang, J.; Luna, R.; Pippel, D.; Rao, N.; Riley, J.P.; Santillan, A.; Savall, B.; Tanis, V.M.; Xue, X.; Young, A.L.
Identification of benzofuran central cores for the inhibition of leukotriene A4 hydrolase
Bioorg. Med. Chem. Lett.
23
811-815
2013
Homo sapiens, Mus musculus
Paz, P.B.; Vega-Hissi, E.G.; Estrada, M.R.; Garro Martinez, J.C.
In silico modeling of the molecular structure and binding of leukotriene A4 into leukotriene A4 hydrolase
Chem. Biol. Drug Des.
80
902-908
2012
Homo sapiens (P09960)
Meng, H.; Liu, Y.; Zhai, Y.; Lai, L.
Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase
Eur. J. Med. Chem.
59
160-167
2013
Homo sapiens
Thangapandian, S.; John, S.; Son, M.; Arulalapperumal, V.; Lee, K.W.
Development of predictive quantitative structure-activity relationship model and its application in the discovery of human leukotriene A4 hydrolase inhibitors
Future Med. Chem.
5
27-40
2013
Homo sapiens
Paz, P.; Vega-Hissi, E.; Andrada, M.; Estrada, M.; Garro Martinez, J.
Quantitative structure activity relationship and binding investigation of N-alkyl glycine amides as inhibitors of Leukotriene A4 hydrolase
Med. Chem. Res.
24
496-504
2015
Homo sapiens (P09960)
-
Thangapandian, S.; John, S.; Lazar, P.; Choi, S.; Lee, K.W.
Structural origins for the loss of catalytic activities of bifunctional human LTA4H revealed through molecular dynamics simulations
PLoS ONE
7
e41063
2012
Homo sapiens
Stsiapanava, A.; Olsson, U.; Wan, M.; Kleinschmidt, T.; Rutishauser, D.; Zubarev, R.A.; Samuelsson, B.; Rinaldo-Matthis, A.; Haeggstroem, J.Z.
Binding of Pro-Gly-Pro at the active site of leukotriene A4 hydrolase/aminopeptidase and development of an epoxide hydrolase selective inhibitor
Proc. Natl. Acad. Sci. USA
111
4227-4232
2014
Homo sapiens (P09960), Homo sapiens
Narendran, G.; Kavitha, D.; Karunaianantham, R.; Gil-Santana, L.; Almeida-Junior, J.L.; Reddy, S.D.; Kumar, M.M.; Hemalatha, H.; Jayanthi, N.N.; Ravichandran, N.; Krishnaraja, R.; Prabhakar, A.; Manoharan, T.; Nithyananthan, L.; Arjunan, G.; Natrajan, M.; Swaminathan, S.; Andrade, B.B.
Role of LTA4H polymorphism in tuberculosis-associated immune reconstitution inflammatory syndrome occurrence and clinical severity in patients infected with HIV
PLoS ONE
11
e0163298
2016
Homo sapiens (P09960), Homo sapiens
Rusznak, M.; Stokes Peebles, R.
Eosinophils express LTA4 hydrolase and synthesize LTB4 important for asthma pathogenesis?
Am. J. Respir. Cell Mol. Biol.
60
375-376
2019
Homo sapiens (P09960)
Snelgrove, R.; Kheradmand, F.
Leukotriene A4 hydrolase the Janus enzyme shows its ugly side in smokers
Am. J. Respir. Crit. Care Med.
190
5-7
2014
Homo sapiens (P09960), Homo sapiens
Vo, T.T.L.; Jang, W.J.; Jeong, C.H.
Leukotriene A4 hydrolase an emerging target of natural products for cancer chemoprevention and chemotherapy
Ann. N. Y. Acad. Sci.
1431
3-13
2018
Homo sapiens (P09960), Mus musculus (P24527), Rattus norvegicus (P30349)
Wittmann, S.K.; Kalinowsky, L.; Kramer, J.S.; Bloecher, R.; Knapp, S.; Steinhilber, D.; Pogoryelov, D.; Proschak, E.; Heering, J.
Thermodynamic properties of leukotriene A4 hydrolase inhibitors
Bioorg. Med. Chem.
24
5243-5248
2016
Homo sapiens (P09960)
El-Naggar, M.H.; Mira, A.; Abdel Bar, F.M.; Shimizu, K.; Amer, M.M.; Badria, F.A.
Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy
Bioorg. Med. Chem.
25
1277-1285
2017
Homo sapiens (P09960), Homo sapiens
Oi, N.; Yamamoto, H.; Langfald, A.; Bai, R.; Lee, M.H.; Bode, A.M.; Dong, Z.
LTA4H regulates cell cycle and skin carcinogenesis
Carcinogenesis
38
728-737
2017
Homo sapiens (P09960), Homo sapiens
Zhao, S.; Yao, K.; Li, D.; Liu, K.; Jin, G.; Yan, M.; Wu, Q.; Chen, H.; Shin, S.H.; Bai, R.; Wang, G.; Bode, A.M.; Dong, Z.; Guo, Z.; Dong, Z.
Inhibition of LTA4H by bestatin in human and mouse colorectal cancer
EBioMedicine
44
361-374
2019
Homo sapiens (P09960), Homo sapiens, Mus musculus (P24527), Mus musculus, Mus musculus C57BL/6J (P24527)
Torres, M.J.; Fierro, A.; Pessoa-Mahana, C.D.; Romero-Parra, J.; Cabrera, G.; Faundez, M.
Effect of alpha lipoic acid on leukotriene A4 hydrolase
Eur. J. Pharmacol.
799
41-47
2017
Homo sapiens (P09960)
Lu, W.; Yao, X.; Ouyang, P.; Dong, N.; Wu, D.; Jiang, X.; Wu, Z.; Zhang, C.; Xu, Z.; Tang, Y.; Zou, S.; Liu, M.; Li, J.; Zeng, M.; Lin, P.; Cheng, F.; Huang, J.
Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis
J. Med. Chem.
60
1817-1828
2017
Homo sapiens (P09960), Homo sapiens, Mus musculus (P24527), Mus musculus
EXTERNAL LINKS (specific for EC-Number 3.3.2.6)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
