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Literature summary for 5.3.2.1 extracted from
- Macrophage migration inhibitory factor (MIF) tautomerase inhibitors as potential novel anti-inflammatory agents: current developments (2009), Curr. Med. Chem., 16, 1091-1114.
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (1E,6E)-1,7-bis(4-hydroxyphenyl)hepta-1,6-diene-3,5-dione | - |
Homo sapiens |  |
| (1E,6E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-1,6-diene-3,5-dione | - |
Homo sapiens | |
| (2E)-2-(2-methoxybenzylidene)cyclopentanone | - |
Homo sapiens | |
| (2E)-2-(3-methoxybenzylidene)cyclopentanone | - |
Homo sapiens | |
| (2E)-2-(4-bromobenzylidene)cyclopentanone | - |
Homo sapiens | |
| (2E)-2-(4-chlorobenzylidene)cyclopentanone | - |
Homo sapiens | |
| (2E)-2-(4-methoxybenzylidene)cyclohexanone | - |
Homo sapiens | |
| (2E)-2-(4-methoxybenzylidene)cyclopentanone | - |
Homo sapiens | |
| (2E)-2-(pyridin-2-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one | - |
Homo sapiens | |
| (2E)-2-(pyridin-3-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one | - |
Homo sapiens | |
| (2E)-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one | - |
Homo sapiens | |
| (2E)-2-benzylidene-3,4-dihydronaphthalen-1(2H)-one | - |
Homo sapiens | |
| (2E)-2-benzylidenecyclohexanone | - |
Homo sapiens | |
| (2E)-2-benzylidenecyclopentanone | - |
Homo sapiens | |
| (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid | - |
Homo sapiens | |
| (2E)-3-(3,4-dioxocyclohexa-1,5-dien-1-yl)prop-2-enoic acid | - |
Homo sapiens | |
| (2E,5E)-2,5-dibenzylidenecyclopentanone | - |
Homo sapiens | |
| (3Z)-3-[4-(dimethylamino)benzylidene]-7-hydroxy-2H-chromene-2,4(3H)-dione | - |
Homo sapiens | |
| (E)-2-fluoro-4-hydroxycinnamate | competitive inhibition | Homo sapiens | |
| (E)-2-fluoro-cinnamate | - |
Homo sapiens | |
| (E)-2-fluorocinnamate | - |
Homo sapiens | |
| (E)-4-hydroxycinnamate | - |
Homo sapiens | |
| (E)-cinnamate | - |
Homo sapiens | |
| (R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester | - |
Homo sapiens | |
| (S)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester | - |
Homo sapiens | |
| (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester | i.e. ISO-I | Homo sapiens | |
| (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid methyl ester | - |
Homo sapiens | |
| (Z)-2-fluoro-4-hydroxycinnamate | - |
Homo sapiens | |
| (Z)-2-fluoro-cinnamate | - |
Homo sapiens | |
| (Z)-2-fluorocinnamate | - |
Homo sapiens | |
| (Z)-4-hydroxycinnamate | - |
Homo sapiens | |
| (Z)-cinnamate | - |
Homo sapiens | |
| 2,2-dimethylpropyl [3-(3-fluoro-4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| 2,2-dimethylpropyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| 2,4,6-trimethylphenyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| 2,5-dibenzylidenecyclopentanone | - |
Homo sapiens | |
| 2-oxo-2-phenylethyl 7-hydroxy-2-oxo-2H-chromene-3-carboxylate | - |
Homo sapiens | |
| 2-oxo-4-phenylbut-3-ynoic acid | inhibition mechanism, overview | Homo sapiens | |
| 2-propionylcyclohexanone | - |
Homo sapiens | |
| 2-[3,6-bis(diethylamino)-3H-xanthen-9-yl]-5-[(6-{[4-({[3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetyl}amino)butyl]amino}-6-oxohexyl)sulfamoyl]benzenesulfonic acid | - |
Homo sapiens | |
| 2-[3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]-N-(4-methoxyphenyl)acetamide | - |
Homo sapiens | |
| 3,4-dihydroxycyclohexa-2,5-diene-1-carboxylic acid | - |
Homo sapiens | |
| 3,4-dioxocyclohexa-1,5-diene-1-carboxylic acid | - |
Homo sapiens | |
| 3,6-dihydroxy-1-methyl-5-oxo-3,5-dihydro-2H-indolium | - |
Homo sapiens | |
| 3,6-dihydroxy-2-methyl-2,3-dihydro-5H-indol-5-one | - |
Homo sapiens | |
| 3,6-dihydroxy-5-oxo-3,5-dihydro-2H-indole-2-carboxylic acid | - |
Homo sapiens | |
| 3-(3,4-dihydroxyphenyl)-7-hydroxy-4H-chromen-4-one | - |
Homo sapiens | |
| 3-acetyl-7-hydroxy-2H-chromen-2-one | - |
Homo sapiens | |
| 3-hydroxy-acetaminophen | - |
Homo sapiens | |
| 3-hydroxybutyrate | - |
Homo sapiens | |
| 3-[4-(1,3-benzodioxol-5-yl)-1,3-thiazol-2-yl]-7-hydroxy-2H-chromen-2-one | - |
Homo sapiens | |
| 4-coumaric acid | - |
Homo sapiens | |
| 4-methoxyphenyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| 4-tert-butylphenyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| 6-hydroxy-2-methyl-5-oxo-3,5-dihydro-2H-indole-2-carboxylic acid | - |
Homo sapiens | |
| 7-hydroxy-2-oxo-2H-chromene-3-carbonitrile | - |
Homo sapiens | |
| 7-hydroxy-2-oxo-2H-chromene-3-carbothioamide | - |
Homo sapiens | |
| 7-hydroxy-3-(2-methyl-1,3-thiazol-4-yl)-2H-chromen-2-one | - |
Homo sapiens | |
| 7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-2H-chromen-2-one | - |
Homo sapiens | |
| 7-hydroxy-3-(pyrazolo[1,5-a]pyridin-2-yl)-2H-chromen-2-one | - |
Homo sapiens | |
| 7-hydroxy-3-phenyl-2H-chromen-2-one | - |
Homo sapiens | |
| 7-hydroxy-3-[4-(2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]-2H-chromen-2-one | - |
Homo sapiens | |
| acetaminophen | - |
Homo sapiens | |
| acetoacetate | - |
Homo sapiens | |
| acetone | - |
Homo sapiens | |
| Acetylacetone | - |
Homo sapiens | |
| AVP-13546 | inhibits the tautomerase activity of MIF and reduces cytokine, including TNF-alpha, levels in vivo | Homo sapiens | |
| boldine | - |
Homo sapiens | |
| butyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| caffeate | - |
Homo sapiens | |
| carnosic acid | - |
Homo sapiens | |
| chlorogenic acid | - |
Homo sapiens | |
| coumarin | - |
Homo sapiens | |
| curcumin | - |
Homo sapiens | |
| cyclohexyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| cyclohexylmethyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| ethyl 3-(7-hydroxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate | - |
Homo sapiens | |
| ethyl 7-hydroxy-2-oxo-2H-chromene-3-carboxylate | inhibition mechanism, overview | Homo sapiens | |
| ethyl acetoacetate | - |
Homo sapiens | |
| ethyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| ferulic acid | - |
Homo sapiens | |
| iodoacetamide | - |
Homo sapiens | |
| methyl 6-hydroxy-2-methyl-5-oxo-3,5-dihydro-2H-indole-2-carboxylate | - |
Homo sapiens | |
| methyl [3-(3-fluoro-4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| additional information | there exist several classes of inhibitors that are active against MIF tautomerase activity, overview. No activity by (S,R)-3-(4-methoxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester and isoxazole and its reduced derivative | Homo sapiens | |
| N-(2,6-dimethyl-4-oxocyclohexa-2,5-dien-1-yl)acetamide | - |
Homo sapiens | |
| N-(3,4-dimethoxyphenyl)acetamide | - |
Homo sapiens | |
| N-(3,5-dimethyl-4-oxocyclohexa-2,5-dien-1-yl)acetamide | - |
Homo sapiens | |
| N-(3-methyl-4-oxocyclohexa-2,5-dien-1-yl)acetamide | - |
Homo sapiens | |
| N-(4-aminobutyl)-2-[3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetamide | - |
Homo sapiens | |
| N-(4-hydroxy-3-methoxycyclohexa-2,5-dien-1-yl)acetamide | - |
Homo sapiens | |
| N-(4-hydroxy-3-methoxyphenyl)acetamide | - |
Homo sapiens | |
| N-acetyl-3-hydroxy-4-benzoquinone imine | - |
Homo sapiens | |
| N-acetyl-4-benzoquinone imine | - |
Homo sapiens | |
| N-cyclohexyl-2-[3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetamide | - |
Homo sapiens | |
| NEM | - |
Homo sapiens | |
| phenyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| phloretin | - |
Homo sapiens | |
| propan-2-yl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| propyl [3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate | - |
Homo sapiens | |
| resveratrol | - |
Homo sapiens | |
| rosmarinic acid | - |
Homo sapiens | |
| tert-butyl [4-({[3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetyl}amino)butyl]carbamate | - |
Homo sapiens | |
| umbelliferone | - |
Homo sapiens | |
| VGX-1027 | - |
Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| keto-(4-hydroxyphenyl)pyruvate | Homo sapiens | - |
enol-(4-hydroxyphenyl)pyruvate | - |
r | |
| keto-phenylpyruvate | Homo sapiens | - |
enol-phenylpyruvate | - |
r | |
| additional information | Homo sapiens | the MIF protein is multifunctional, exhibiting besides its tautomerase activity, e.g. also L-dopachrome isomerase activity, EC 5.3.3.12, and thioredoxin-like function, or its cytokine function, overview | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| endothelial cell | - |
Homo sapiens | - |
| eosinophil | - |
Homo sapiens | - |
| macrophage | - |
Homo sapiens | - |
| pituitary gland | corticotrop cells | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| keto-(4-hydroxyphenyl)pyruvate | - |
Homo sapiens | enol-(4-hydroxyphenyl)pyruvate | - |
r | |
| keto-phenylpyruvate | - |
Homo sapiens | enol-phenylpyruvate | - |
r | |
| additional information | the MIF protein is multifunctional, exhibiting besides its tautomerase activity, e.g. also L-dopachrome isomerase activity, EC 5.3.3.12, and thioredoxin-like function, or its cytokine function, overview | Homo sapiens | ? | - |
? | |
| additional information | the N-terminal Pro is essential for the tautomerase activity of MIF | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| trimer | the tertiary structure is stabilized by hydrogen bonds and a hydrophobic core, three beta-sheets and six alpha-helices surround a traversing channel with dominant positive charge in the middle of the trimer, structure, overview. The enzyme contains a Cys-Xaa-Xaa-Cys motif required for oxido-reductase activity and MIF-like activities like glucorticoid overriding and cell proliferation | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| macrophage migration inhibitory factor tautomerase | - |
Homo sapiens |
| MIF tautomerase | - |
Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000038 | - |
- |
Homo sapiens | 3-(3,4-dihydroxyphenyl)-7-hydroxy-4H-chromen-4-one | |
| 0.00028 | - |
- |
Homo sapiens | 7-hydroxy-3-[4-(2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]-2H-chromen-2-one | |
| 0.00047 | - |
- |
Homo sapiens | 7-hydroxy-3-phenyl-2H-chromen-2-one | |
| 0.0005 | - |
- |
Homo sapiens | 7-hydroxy-3-(pyrazolo[1,5-a]pyridin-2-yl)-2H-chromen-2-one | |
| 0.00055 | - |
- |
Homo sapiens | 7-hydroxy-2-oxo-2H-chromene-3-carbothioamide | |
| 0.0007 | - |
- |
Homo sapiens | N-acetyl-3-hydroxy-4-benzoquinone imine | |
| 0.0013 | - |
- |
Homo sapiens | AVP-13546 | |
| 0.0015 | - |
- |
Homo sapiens | (E)-4-hydroxycinnamate | |
| 0.0015 | - |
- |
Homo sapiens | 3-[4-(1,3-benzodioxol-5-yl)-1,3-thiazol-2-yl]-7-hydroxy-2H-chromen-2-one | |
| 0.0016 | - |
- |
Homo sapiens | 2-oxo-2-phenylethyl 7-hydroxy-2-oxo-2H-chromene-3-carboxylate | |
| 0.00161 | - |
- |
Homo sapiens | 2,5-dibenzylidenecyclopentanone | |
| 0.0021 | - |
- |
Homo sapiens | 7-hydroxy-3-(2-methyl-1,3-thiazol-4-yl)-2H-chromen-2-one | |
| 0.0026 | - |
- |
Homo sapiens | (E)-2-fluoro-4-hydroxycinnamate | |
| 0.0029 | - |
- |
Homo sapiens | 7-hydroxy-2-oxo-2H-chromene-3-carbonitrile | |
| 0.0031 | - |
- |
Homo sapiens | 7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-2H-chromen-2-one | |
| 0.0043 | - |
- |
Homo sapiens | 3-acetyl-7-hydroxy-2H-chromen-2-one | |
| 0.0058 | - |
- |
Homo sapiens | ethyl 3-(7-hydroxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate | |
| 0.0062 | - |
- |
Homo sapiens | (3Z)-3-[4-(dimethylamino)benzylidene]-7-hydroxy-2H-chromene-2,4(3H)-dione | |
| 0.007 | - |
- |
Homo sapiens | (R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester | |
| 0.0074 | - |
- |
Homo sapiens | ethyl 7-hydroxy-2-oxo-2H-chromene-3-carboxylate | |
| 0.013 | - |
- |
Homo sapiens | (S)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester | |
| 0.04 | - |
- |
Homo sapiens | N-acetyl-4-benzoquinone imine | |
| 0.073 | - |
- |
Homo sapiens | (E)-2-fluoro-cinnamate | |
| 0.073 | - |
- |
Homo sapiens | (E)-2-fluorocinnamate | |
| 0.21 | - |
- |
Homo sapiens | (Z)-4-hydroxycinnamate | |
| 0.48 | - |
- |
Homo sapiens | (Z)-2-fluoro-4-hydroxycinnamate | |
| 0.5 | - |
- |
Homo sapiens | 3-hydroxy-acetaminophen | |
| 2.33 | - |
- |
Homo sapiens | (Z)-2-fluorocinnamate | |
| 2.33 | - |
- |
Homo sapiens | (Z)-2-fluoro-cinnamate | |
| 10 | - |
- |
Homo sapiens | acetaminophen | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | MIF expression is upregulated by cytokines, TNF-alpha and interleukin-I, and by bacterial endotoxins, such as lipopolysaccharides, and exotoxins | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | MIF expression contributes to cell proliferation, invasiveness and neo-angiogenesis of neuroblastoma, gastric, hepatocellularbladder, and breast carcinomas. MIF takes part in the pathogenesis of Alzheimer's disease and multiple sklerosis | Homo sapiens |
| physiological function | MIF plays an essential role in both, innate and adaptive immune response. It is implicated in tumor growth and angiogenesis, an exerts an antagonistic effect against glucocorticoid immunosuppressive action, and shows glucorticoid overriding activity | Homo sapiens |
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