Literature summary for 1.14.11.30 extracted from

Flagg, S.C.; Martin, C.B.; Taabazuing, C.Y.; Holmes, B.E.; Knapp, M.J.
Screening chelating inhibitors of HIF-prolyl hydroxylase domain 2 (PHD2) and factor inhibiting HIF (FIH) (2012), J. Inorg. Biochem., 113, 25-30.

Search for more literature for 1.14.11.30

Activating Compound

Activating Compound	Comment	Organism	Structure
ascorbate	-	Homo sapiens

Application

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(Commentary)

Cloned (Comment)	Organism
expression of N-terminally His-tagged FIH-1 in Escherichia coli strain BL21(DE3)	Homo sapiens

Inhibitors

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 [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.022	-	2-oxoglutarate	pH 7.0, 37°C	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Fe2+	dependent on, non-heme iron	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Substrates and Products (Substrate)

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

Synonyms	Comment	Organism
factor inhibiting HIF	-	Homo sapiens
FIH	-	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	-	assay at	Homo sapiens

IC50 Value

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

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Release 2023.1 (January 2023)