Activating Compound | Comment | Organism | Structure |
---|---|---|---|
ascorbate | - |
Homo sapiens |
Application | Comment | Organism |
---|---|---|
drug development | the unique function of FIH makes it a prime target for selective inhibition leading to regulatory control of diseases such as cancer and stroke | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of N-terminally His-tagged FIH-1 in Escherichia coli strain BL21(DE3) | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2,3-dihydroxypyridine | - |
Homo sapiens | |
2-hydroxypyridine 1-oxide | - |
Homo sapiens | |
3-cyano-6-methyl-2(H)-pyridinone | - |
Homo sapiens | |
3-hydroxy-1,2-dimethyl-4(1H)-pyridinone | - |
Homo sapiens | |
3-hydroxy-2-methyl-4-pyrone | - |
Homo sapiens | |
4-methylcatechol | - |
Homo sapiens | |
4-nitrocatechol | - |
Homo sapiens | |
4-tert-butylcatechol | - |
Homo sapiens | |
5-hydroxy-2-hydroxymethyl-4-pyrone | - |
Homo sapiens | |
5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid | - |
Homo sapiens | |
additional information | screening of iron chelators pyridines, hydroxypyrones/hydroxypyridinones, and catechols as inhibitors for FIH, analysis of selectivity of the inhibitors for FIH compared to PHD2, EC 1.14.11.29. Ligand binding kinetics and structural analysis, overview. Representative inhibitors bind to the metal center in both FIH as an 2-oxoglutarate mimic | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.022 | - |
2-oxoglutarate | pH 7.0, 37°C | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | dependent on, non-heme iron | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 | Homo sapiens | FIH hydroxylates Asn803 of HIF-1alpha | hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 | FIH hydroxylates Asn803 of HIF-1alpha | Homo sapiens | hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-asparagine peptide + 2-oxoglutarate + O2 | 39-residue peptide corresponding to HIF-1alpha788-826 mutant C800A | Homo sapiens | hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine peptide + succinate + CO2 | hydroxylation at Asn803 | ? |
Synonyms | Comment | Organism |
---|---|---|
factor inhibiting HIF | - |
Homo sapiens |
FIH | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.01 | - |
pH 7.0, 37°C | Homo sapiens | 4-nitrocatechol | |
0.01 | - |
pH 7.0, 37°C | Homo sapiens | 2-hydroxypyridine 1-oxide | |
0.03 | - |
pH 7.0, 37°C | Homo sapiens | 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone | |
0.05 | - |
pH 7.0, 37°C | Homo sapiens | 4-methylcatechol | |
0.05 | - |
pH 7.0, 37°C | Homo sapiens | 5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid | |
0.07 | - |
above, pH 7.0, 37°C | Homo sapiens | 3-hydroxy-2-methyl-4-pyrone | |
0.075 | - |
pH 7.0, 37°C | Homo sapiens | 2,3-dihydroxypyridine | |
0.12 | - |
pH 7.0, 37°C | Homo sapiens | 4-tert-butylcatechol | |
0.17 | - |
pH 7.0, 37°C | Homo sapiens | 5-hydroxy-2-hydroxymethyl-4-pyrone | |
1 | - |
above, pH 7.0, 37°C | Homo sapiens | 3-cyano-6-methyl-2(H)-pyridinone |