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Literature summary for 1.13.11.34 extracted from
- Further studies on ethyl 5-hydroxy-indole-3-carboxylate scaffold design, synthesis and evaluation of 2-phenylthiomethyl-indole derivatives as efficient inhibitors of human 5-lipoxygenase (2014), Eur. J. Med. Chem., 81, 492-498 .
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | the enzyme is an attractive drug target for the pharmacotherapy of inflammatory and allergic diseases | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene alox5, recombinant expression in Escherichia coli strain BL21 | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| ethyl 2-((2,4-difluorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens |  |
| ethyl 2-((2,6-dichlorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 2-((2,6-dimethylphenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 2-((3,5-dimethylphenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 2-((3-chlorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 2-((4-fluorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 2-[(3-chlorophenyl)-amino]-5-hydroxy-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-1-methyl-2-((2-(trifluoromethyl)phenylthio)methyl)-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-1-methyl-2-((4-(trifluoromethoxy)phenylthio)methyl)-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-1-methyl-2-((4-(trifluoromethyl)phenylthio)methyl)-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-1-methyl-2-(phenylthiomethyl)-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-2-((2-methoxyphenylthio)methyl)-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-2-((4-methoxyphenylthio)methyl)-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| ethyl 5-hydroxy-2-(mesitylthiomethyl)-1-methyl-1H-indole-3-carboxylate | - |
Homo sapiens | |
| additional information | design, synthesis, and evaluation of 2-phenylthiomethyl-indole derivatives from an ethyl 5-hydroxy-indole-3-carboxylate scaffold as efficient inhibitors of human 5-lipoxygenase, structure-activity relationships, overview. The potency of compounds is closely related to the positioning of the substituents at the phenylthiomethyl ring. The introduction of methyl or chlorine groups in ortho- and ortho/para-position of thiophenol represent the most favorable modifications. Among all tested compounds, ethyl 5-hydroxy-2-(mesitylthiomethyl)-1-methyl-1H-indole-3-carboxylate is the most potent derivative which blocks 5-LO activity in cell-free assays and suppresses 5-LO product synthesis in polymorphonuclear leukocytes. The compounds are not active against 12-LO and 15-LO, EC 1.13.11.31 and EC 1.13.11.33 | Homo sapiens | |
| zileuton | - |
Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate | Homo sapiens | epoxidation | (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? | |
| arachidonate + O2 | Homo sapiens | hydroperoxidation | (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate | - |
? | |
| arachidonate + O2 | Homo sapiens | overall reaction | (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 by ATP affinity chromatography | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| leukocyte | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate | epoxidation | Homo sapiens | (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? | |
| arachidonate + O2 | hydroperoxidation | Homo sapiens | (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate | - |
? | |
| arachidonate + O2 | overall reaction | 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 |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.0003 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-[(3-chlorophenyl)-amino]-5-hydroxy-1H-indole-3-carboxylate | |
| 0.0007 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-2-(mesitylthiomethyl)-1-methyl-1H-indole-3-carboxylate | |
| 0.0008 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-1-methyl-2-((2-(trifluoromethyl)phenylthio)methyl)-1H-indole-3-carboxylate | |
| 0.0008 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-((2,6-dichlorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | |
| 0.0008 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-((2,6-dimethylphenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | |
| 0.0009 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-1-methyl-2-((4-(trifluoromethoxy)phenylthio)methyl)-1H-indole-3-carboxylate | |
| 0.0018 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-((3,5-dimethylphenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | |
| 0.0023 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-2-((4-methoxyphenylthio)methyl)-1-methyl-1H-indole-3-carboxylate | |
| 0.0029 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-2-((2-methoxyphenylthio)methyl)-1-methyl-1H-indole-3-carboxylate | |
| 0.0032 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-((2,4-difluorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | |
| 0.0038 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-((3-chlorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | |
| 0.0042 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-1-methyl-2-((4-(trifluoromethyl)phenylthio)methyl)-1H-indole-3-carboxylate | |
| 0.005 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 2-((4-fluorophenylthio)methyl)-5-hydroxy-1-methyl-1H-indole-3-carboxylate | |
| 0.0057 | - |
pH 7.4, 37°C, cell-free enzyme extract | Homo sapiens | ethyl 5-hydroxy-1-methyl-2-(phenylthiomethyl)-1H-indole-3-carboxylate | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | 5-lipoxygenase enzyme catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes | Homo sapiens |
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