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Literature summary extracted from

  • Koeberle, A.; Zettl, H.; Greiner, C.; Wurglics, M.; Schubert-Zsilavecz, M.; Werz, O.
    Pirinixic acid derivatives as novel dual inhibitors of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase (2008), J. Med. Chem., 51, 8068-8076.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.13.11.34 additional information Ca2+-ionophore A23187 Homo sapiens

Application

EC Number Application Comment Organism
1.13.11.34 drug development pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-lipoxygenase inhibitors with a promising pharmacologial profile and a potential for therapeutic use Homo sapiens
5.3.99.3 medicine mPGES-1 is a potential target for inhibitors, pathological conditions, such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis are related to elevated levels of PGE2 Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.13.11.34 Escherichia coli MV1190 transformed with pT3-5LO plasmid Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.13.11.34 (E)-N-hydroxy-N-(3-(3-phenoxyphenyl)-allyl)acetamide BWA4C Homo sapiens
1.13.11.34 ([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)(naphthalen-1-yl)acetic acid
-
 Homo sapiens
1.13.11.34 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidine-2-ylthio)octanoic acid
-
 Homo sapiens
1.13.11.34 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid
-
 Homo sapiens
1.13.11.34 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)acetic acid
-
 Homo sapiens
1.13.11.34 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoic acid
-
 Homo sapiens
1.13.11.34 2-(4-chloro-6-(5-methoxy-2-methylbiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoic acid
-
 Homo sapiens
1.13.11.34 2-([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)octanoic acid
-
 Homo sapiens
1.13.11.34 2-[(4-[[3,5-bis(2,2,2-trifluoroethoxy)phenyl]amino]-6-chloropyrimidin-2-yl)sulfanyl]octanoic acid
-
 Homo sapiens
1.13.11.34 ethyl 2-[[4-chloro-6-(quinolin-6-ylamino)pyrimidin-2-yl]sulfanyl]octanoate
-
 Homo sapiens
1.13.11.34 additional information class of dual microsomal PGE2 synthase-1/5-lipoxygenase inhibitors based on the structure of pirinixic acid. Target oriented structural modification of pirinixic acid, particularly R substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2,3-dimethylaniline by a biphenyl-4-yl-methane-amino residue, results in potent suppression of mPGES-1 and 5-lipoxygenase activity. Is not inhibited by 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-isopropyl-1H-indol-2-yl)-2,2-dimethylpropanoic acid Homo sapiens
1.13.11.34 N-hydroxy-N-[(2E)-3-(3-phenoxyphenyl)prop-2-en-1-yl]acetamide
-
 Homo sapiens
5.3.99.3 ([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)(5,8-dihydronaphthalen-1-yl)acetic acid
-
 Homo sapiens
5.3.99.3 2-([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)nonanoic acid
-
 Homo sapiens
5.3.99.3 2-([4-chloro-6-[(4'-cyanobiphenyl-4-yl)amino]pyrimidin-2-yl]sulfanyl)nonanoic acid
-
 Homo sapiens
5.3.99.3 2-([4-chloro-6-[(5-methoxy-2-methylbiphenyl-4-yl)amino]pyrimidin-2-yl]sulfanyl)nonanoic acid
-
 Homo sapiens
5.3.99.3 2-([4-[(biphenyl-4-ylmethyl)amino]-6-chloropyrimidin-2-yl]sulfanyl)nonanoic acid
-
 Homo sapiens
5.3.99.3 2-[(4-[[3,5-bis(2,2,2-trifluoroethoxy)phenyl]amino]-6-chloropyrimidin-2-yl)sulfanyl]nonanoic acid
-
 Homo sapiens
5.3.99.3 2-[[4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-yl]sulfanyl]nonanoic acid
-
 Homo sapiens
5.3.99.3 3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(1-methylethyl)-1H-indol-2-yl]-2,2-dimethylpropanoic acid
-
 Homo sapiens
5.3.99.3 ethyl 2-[[4-chloro-6-(quinolin-6-ylamino)pyrimidin-2-yl]sulfanyl]nonanoate
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5.3.99.3 (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate Homo sapiens
-
 (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.13.11.34 Homo sapiens
-
-
-
5.3.99.3 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.13.11.34 partially purified by sonication, centrifugation and gel filtration Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.13.11.34 polymorphonuclear leukocyte
-
 Homo sapiens
-
5.3.99.3 A-549 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.13.11.34 arachidonate + O2
-
 Homo sapiens (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoate
-
 ?
5.3.99.3 (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
 Homo sapiens (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.13.11.34 5-lipoxygenase
-
 Homo sapiens
1.13.11.34 5-LO
-
 Homo sapiens
5.3.99.3 microsomal prostaglandin E2 synthase-1
-
 Homo sapiens
5.3.99.3 mPGES-1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
5.3.99.3 4
-
 microsomal membranes are incubated with PGH2, enzyme activity assay Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
5.3.99.3 7.4
-
 microsomal membranes are incubated with PGH2, enzyme activity assay Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.13.11.34 0.00011
-
 in intact polymorphonuclear leukocytes Homo sapiens N-hydroxy-N-[(2E)-3-(3-phenoxyphenyl)prop-2-en-1-yl]acetamide
1.13.11.34 0.00016
-
 purified 5-lipoxygenase Homo sapiens N-hydroxy-N-[(2E)-3-(3-phenoxyphenyl)prop-2-en-1-yl]acetamide
1.13.11.34 0.0004
-
 in intact polymorphonuclear leukocytes Homo sapiens 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoic acid
1.13.11.34 0.0005
-
 in intact polymorphonuclear leukocytes Homo sapiens 2-(4-chloro-6-(5-methoxy-2-methylbiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoic acid
1.13.11.34 0.0006
-
 in intact polymorphonuclear leukocytes Homo sapiens ethyl 2-[[4-chloro-6-(quinolin-6-ylamino)pyrimidin-2-yl]sulfanyl]octanoate
1.13.11.34 0.0007
-
 in intact polymorphonuclear leukocytes Homo sapiens 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidine-2-ylthio)octanoic acid
1.13.11.34 0.001
-
 in intact polymorphonuclear leukocytes Homo sapiens 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid
1.13.11.34 0.0015
-
 in intact polymorphonuclear leukocytes Homo sapiens 2-[(4-[[3,5-bis(2,2,2-trifluoroethoxy)phenyl]amino]-6-chloropyrimidin-2-yl)sulfanyl]octanoic acid
1.13.11.34 0.0015
-
 purified 5-lipoxygenase Homo sapiens 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidine-2-ylthio)octanoic acid
1.13.11.34 0.0015
-
 purified 5-lipoxygenase Homo sapiens 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoic acid
1.13.11.34 0.002
-
 purified 5-lipoxygenase Homo sapiens 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid
1.13.11.34 0.002
-
 purified 5-lipoxygenase Homo sapiens 2-(4-chloro-6-(5-methoxy-2-methylbiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoic acid
1.13.11.34 0.003
-
 purified 5-lipoxygenase Homo sapiens 2-[(4-[[3,5-bis(2,2,2-trifluoroethoxy)phenyl]amino]-6-chloropyrimidin-2-yl)sulfanyl]octanoic acid
1.13.11.34 0.0041
-
 in intact polymorphonuclear leukocytes Homo sapiens 2-([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)octanoic acid
1.13.11.34 0.005
-
 in intact polymorphonuclear leukocytes Homo sapiens ([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)(naphthalen-1-yl)acetic acid
1.13.11.34 0.0065
-
 purified 5-lipoxygenase Homo sapiens 2-([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)octanoic acid
1.13.11.34 0.019
-
 purified 5-lipoxygenase Homo sapiens ethyl 2-[[4-chloro-6-(quinolin-6-ylamino)pyrimidin-2-yl]sulfanyl]octanoate
5.3.99.3 0.0013
-
-
 Homo sapiens 2-([4-[(biphenyl-4-ylmethyl)amino]-6-chloropyrimidin-2-yl]sulfanyl)nonanoic acid
5.3.99.3 0.0016
-
-
 Homo sapiens 2-[[4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-yl]sulfanyl]nonanoic acid
5.3.99.3 0.0017
-
-
 Homo sapiens 2-([4-chloro-6-[(4'-cyanobiphenyl-4-yl)amino]pyrimidin-2-yl]sulfanyl)nonanoic acid
5.3.99.3 0.0021
-
-
 Homo sapiens 2-([4-chloro-6-[(5-methoxy-2-methylbiphenyl-4-yl)amino]pyrimidin-2-yl]sulfanyl)nonanoic acid
5.3.99.3 0.0021
-
-
 Homo sapiens 3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(1-methylethyl)-1H-indol-2-yl]-2,2-dimethylpropanoic acid
5.3.99.3 0.0026
-
-
 Homo sapiens 2-[(4-[[3,5-bis(2,2,2-trifluoroethoxy)phenyl]amino]-6-chloropyrimidin-2-yl)sulfanyl]nonanoic acid
5.3.99.3 0.0039
-
-
 Homo sapiens 2-([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)nonanoic acid
5.3.99.3 0.0051
-
-
 Homo sapiens ([4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl]sulfanyl)(5,8-dihydronaphthalen-1-yl)acetic acid
5.3.99.3 0.0056
-
-
 Homo sapiens ethyl 2-[[4-chloro-6-(quinolin-6-ylamino)pyrimidin-2-yl]sulfanyl]nonanoate