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Literature summary for 1.13.11.34 extracted from

  • Kretschmer, S.B.M; Woltersdorf, S.; Vogt, D.; Lillich, F.F.; Ruehl, M.; Karas, M.; Maucher, I.V.; Roos, J.; Haefner, A.-K.; Kaiser, A.; Wurglics, M.; Schubert-Zsilavecz, M.; Angioni, C.; Geisslinger, G.; Stark, H.; Steinhilber, D.; Hofmann, B.
    Characterization of the molecular mechanism of 5-lipoxygenase inhibition by 2-aminothiazoles (2017), Biochem. Pharmacol., 123, 52-62 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

Protein Variants

Protein Variants Comment Organism
C159S site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme Homo sapiens
C300S site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme Homo sapiens
C416S site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme Homo sapiens
C418S site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
4-(4-(4-chlorophenyl)thiazol-2-ylimino)cyclohexa-2,5-dienone ST-1905 Homo sapiens
4-[(4-cyclohexyl-5-methyl-1,3-thiazol-2-yl)amino]-2,6-dimethylphenol lead compound, in vitro pharmacokinetic profile, shows no cytotoxicity, overview Homo sapiens
4-[[4-(2,4-dichlorophenyl)-5-methyl-1,3-thiazol-2-yl]amino]-2,6-dimethylphenol lead compound, in vitro pharmacokinetic profile, shows no cytotoxicity, overview Homo sapiens
4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol
-
Homo sapiens
4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]imino]cyclohexa-2,5-dien-1-one
-
Homo sapiens
BWA-4C
-
Homo sapiens
additional information molecular mechanism of 5-lipoxygenase inhibition by 2-aminothiazoles, overview. ST-1083 and ST-1905, but not the lead compounds, show covalent binding to 5-LO and the potency of ST-1083 and ST-1905, but not of the lead compounds is impaired for 5-LO cysteine mutants. Especially the cysteines 159, 300, 416, and 418, located in the substrate entry channel of 5-LO, are prone to be potential targets for inhibition. The lead compounds show no dependency on thiol level Homo sapiens
U73122
-
Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ required, iron reduction from Fe3+ to Fe2+ during catalyis Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
arachidonate + O2 Homo sapiens
-
(5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P09917
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, and anion exchange chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
Hep-G2 cell
-
Homo sapiens
-
leukocyte polymorphonuclear Homo sapiens
-
U-937 cell leukemic monocyte cells Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
arachidonate + O2
-
Homo sapiens (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
-
?

Synonyms

Synonyms Comment Organism
5-lipoxygenase
-
Homo sapiens
5-LO
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00003
-
pH 7.4, 37°C, recombinant enzyme Homo sapiens 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol
0.00004
-
pH 7.4, 37°C, recombinant enzyme Homo sapiens 4-(4-(4-chlorophenyl)thiazol-2-ylimino)cyclohexa-2,5-dienone

General Information

General Information Comment Organism
physiological function 5-lipoxygenase is implicated in the pathogenesis of inflammatory and immune diseases Homo sapiens