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Literature summary 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)

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

Protein Variants

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.13.11.34 4-(4-(4-chlorophenyl)thiazol-2-ylimino)cyclohexa-2,5-dienone ST-1905 Homo sapiens
1.13.11.34 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
1.13.11.34 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
1.13.11.34 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol
-
 Homo sapiens
1.13.11.34 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]imino]cyclohexa-2,5-dien-1-one
-
 Homo sapiens
1.13.11.34 BWA-4C
-
 Homo sapiens
1.13.11.34 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
1.13.11.34 U73122
-
 Homo sapiens

Metals/Ions

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

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
1.13.11.34 Homo sapiens P09917
-
-

Purification (Commentary)

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

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.13.11.34 Hep-G2 cell
-
 Homo sapiens
-
1.13.11.34 leukocyte polymorphonuclear Homo sapiens
-
1.13.11.34 U-937 cell leukemic monocyte cells 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 (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.13.11.34 5-lipoxygenase
-
 Homo sapiens
1.13.11.34 5-LO
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.13.11.34 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.13.11.34 7.4
-
 assay at Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.13.11.34 0.00003
-
 pH 7.4, 37°C, recombinant enzyme Homo sapiens 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol
1.13.11.34 0.00004
-
 pH 7.4, 37°C, recombinant enzyme Homo sapiens 4-(4-(4-chlorophenyl)thiazol-2-ylimino)cyclohexa-2,5-dienone

General Information

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