1.14.11.29 (2R)-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido](phenyl)acetic acid - 220895 1.14.11.29 (2S)-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido](phenyl)acetic acid - 220894 1.14.11.29 1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol noncompetitive inhibition 15364 1.14.11.29 1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol chelates Fe2+ in a hexacoordinative mode through four nitrogens of the macrocycle and two oxygens in side arms 15364 1.14.11.29 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid i.e. JNJ-42041935, 2-oxoglutarate analogue 262344 1.14.11.29 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetamide chelates Fe2+ in a hexacoordinative mode through four nitrogens of the macrocycle and two oxygens in side arms 42540 1.14.11.29 2,3-dihydroxypyridine - 13246 1.14.11.29 2-(2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methylthiazol-4-yl)-N-(2-(diethylamino)ethyl)acetamide - 220908 1.14.11.29 2-(2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-phenylthiazol-4-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide - 220904 1.14.11.29 2-(2-(5-cyano-3-hydroxypyridin-2-yl)-5-phenylthiazol-4-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide - 220901 1.14.11.29 2-hydroxypyridine 1-oxide - 28998 1.14.11.29 2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(diethylamino)ethyl]acetamide - 220907 1.14.11.29 2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide - 220902 1.14.11.29 2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-propylacetamide - 220905 1.14.11.29 2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide - 220903 1.14.11.29 2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-(2-phenylethyl)acetamide - 220898 1.14.11.29 2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide - 220896 1.14.11.29 2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[(1S)-2-hydroxy-1-phenylethyl]acetamide - 220897 1.14.11.29 2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide - 220899 1.14.11.29 2-[2-(5-cyano-3-hydroxypyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide - 220900 1.14.11.29 2-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido]-2-methylpropanoic acid - 220893 1.14.11.29 3,3'-[(pyridin-2-ylmethyl)imino]dipropanenitrile noncompetitive inhibition 42539 1.14.11.29 3,3'-[(pyridin-4-ylimino)bis(propane-3,1-diyliminomethanediyl)]diphenol noncompetitive inhibition 42538 1.14.11.29 3,3'-[(pyridin-4-ylimino)bis[propane-3,1-diylnitrilo(Z)methylylidene]]diphenol noncompetitive inhibition 42537 1.14.11.29 3,4-dihydroxybenzoate - 736 1.14.11.29 3,6,9-tris(naphthalen-1-ylmethyl)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene coordinates Fe2+ via triad or tetrad from nitrogen atoms of the parent ring, which leaves vacant position for other ligands binding 42541 1.14.11.29 3-([1,1'-biphenyl]-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-1-(pyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione compound stabilizes HIF-1alpha levels and is also active against lysine-specific demethylase KDM4A 261304 1.14.11.29 3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline - 4694 1.14.11.29 3-cyano-6-methyl-2(H)-pyridinone - 28997 1.14.11.29 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone - 29002 1.14.11.29 3-hydroxy-2-methyl-4-pyrone - 29001 1.14.11.29 3-hydroxypyridine-2-carbonyl-glycine - 4382 1.14.11.29 3-[(1,3-benzoxazol-2-yl)carbamoyl]propanoic acid - 261324 1.14.11.29 3-[(5-chloro-1,3-benzoxazol-2-yl)carbamoyl]propanoic acid - 261334 1.14.11.29 4-hydroxy-2-(1H-pyrazol-1-yl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-5-carboxamide - 261464 1.14.11.29 4-hydroxy-N-[(1R)-2-hydroxy-1-phenylethyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide - 261470 1.14.11.29 4-hydroxy-N-[(4-phenoxyphenyl)methyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide - 261471 1.14.11.29 4-methylcatechol - 376 1.14.11.29 4-nitrocatechol - 1492 1.14.11.29 4-tert-butylcatechol - 3400 1.14.11.29 5-hydroxy-2-hydroxymethyl-4-pyrone - 28999 1.14.11.29 5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid - 29000 1.14.11.29 5-hydroxy-6-[4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]-1,3-thiazol-2-yl]pyridine-3-carbonitrile - 220906 1.14.11.29 6-[5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl]pyridine-3-carboxylic acid - 220865 1.14.11.29 7-[(4-chlorophenyl)[(3-hydroxypyridin-2-yl)amino]methyl]quinolin-8-ol - 220873 1.14.11.29 adaptaquin - 262346 1.14.11.29 adaptaquin EC50 of ca 2 mM in HIF1 ODD-luc fusion reporter assay 262346 1.14.11.29 AKB-6548 - 220882 1.14.11.29 BAY85-3934 - 220885 1.14.11.29 ciclopirox - 13273 1.14.11.29 ciclopirox iron chelator 13273 1.14.11.29 ciclopirox olamine - 14621 1.14.11.29 CO releasing molecule-2 i.e.CORM-2, [RuCl2(CO)3]2, in situ CO donor, reduces the hydroxylation of C-terminal and N-terminal oxygen-dependent degradation domains of HIF-1alpha 262347 1.14.11.29 cobalt chloride - 151966 1.14.11.29 Cu2+ binding analysis 19 1.14.11.29 Cu2+ - 19 1.14.11.29 deferoxamine - 23293 1.14.11.29 desferrioxamine iron chelator 4808 1.14.11.29 dimethyloxalyl glycine mimicks 2-oxoglutarate binding mode 262345 1.14.11.29 dimethyloxalylglycine - 21832 1.14.11.29 dimethyloxalylglycine 2-oxoglutarate analogue 21832 1.14.11.29 DLDLEALA-L-3,4-dehydroproline-YIPADDDFQLR - 174483 1.14.11.29 DLDLEALA-L-4-thioproline-YIPADDDFQLR - 174484 1.14.11.29 DLDLEALA-L-piperidine-2-carboxylic acid-YIPADDDFQLR - 174482 1.14.11.29 DLDLEALA-L-trans-4-fluoroproline-YIPADDDFQLR - 174480 1.14.11.29 DLDLEALA-L-trans-4-hydroxyproline-YIPADDDFQLR - 174481 1.14.11.29 ethyl 3,4-dihydroxybenzoate iron chelator that can fit inside the active center 32633 1.14.11.29 FG-0041 - 220881 1.14.11.29 FG-2216 - 220874 1.14.11.29 FG-4497 - 220875 1.14.11.29 FG-4592 - 220871 1.14.11.29 FG-4592 mimicks 2-oxoglutarate binding mode 220871 1.14.11.29 FG-4592 i.e. roxadustat 220871 1.14.11.29 FG-4592 i.e. roxadustat, 2-oxoglutarate analogue 220871 1.14.11.29 FKBP38 - 220879 1.14.11.29 GSK1278863 - 220884 1.14.11.29 GSK360A - 220876 1.14.11.29 H2O2 poor inhibition. Prolyl hydroxylase is less sensitive to peroxide, preferential inhibition of N803-hydroxylation by FIH, EC 1.14.11.30, compared with inhibition of P402/P564 hydroxylation by PHDs 22 1.14.11.29 IOX2 mimicks 2-oxoglutarate binding mode 261882 1.14.11.29 JNJ1935 a prolyl-hydroxylase selective inhibitor. Low concentrations of JNJ1935 selectively inhibit PHDs, whereas higher concentrations inhibit all hydroxylases, including FIH, EC 1.14.11.30, in vitro and in vivo inhibition 174479 1.14.11.29 L-mimosine - 2850 1.14.11.29 Mn2+ - 11 1.14.11.29 additional information the peptide inhibitors consist of amino acids identical to those in the CODD556-575 except the 564 proline residue, and target the C-terminal oxygen-dependent degradation domain binding site in the PHD2 active pocket. Specific inhibition of PHD2, no inhibition of FIH, EC 1.14.11.30 2 1.14.11.29 additional information temporal dynamics of hydroxylase inhibition, overview 2 1.14.11.29 additional information polynitrogen compound as HIF-1alpha PHD3 inhibitors, the metal complexes of these polynitrogen compounds cannot inhibit the catalytical activity of PHD3, overview. The inhibitory mechanism of PHD3 activity by polynitrogen compounds is due to their binding to iron to form stable coordination complexes 2 1.14.11.29 additional information screening of iron chelators pyridines, hydroxypyrones/hydroxypyridinones, and catechols as inhibitors for PHD2, analysis of selectivity of the inhibitors for PHD2 compared to FIH, EC 1.14.11.30. Ligand binding kinetics and structural analysis, overview. Representative inhibitors bind to the metal center in PHD2 as an 2-oxoglutarate mimic 2 1.14.11.29 additional information inhibition of the recombinant human PHD3 activity by tetraazamacrocycles, overview 2 1.14.11.29 additional information compounds with a 3-carbamoylpropanoic acids-containing benzoxazole moiety are inhibitors of PHD-2. However, neither the acids nor their respective ethyl esters upregulate HIF-1alpha levels in cells 2 1.14.11.29 Morg-1 - 220880 1.14.11.29 N,N-dimethyl-5-[3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-ylsulfonyl]naphthalen-1-amine coordinates Fe2+ via triad or tetrad from nitrogen atoms of the parent ring, which leaves vacant position for other ligands binding 42542 1.14.11.29 N-((3,4-dimethoxyphenyl)(8-hydroxyquinolin-7-yl)methyl)-2-phenylacetamide - 220872 1.14.11.29 N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine - 7813 1.14.11.29 N-(1-[[6-(4-chlorophenoxy)pyridin-3-yl]methyl]-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine clinical candidate as PHD2 inhibitor, promotes the production of erythropoietin following oral administration in mice and rats. The predicted half-life in humans is 1.3-5.6 h 261932 1.14.11.29 N-(4-hydroxy-1-[[4-(4-methylphenoxy)phenyl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine - 261956 1.14.11.29 N-(4-hydroxy-1-[[5-(4-methylphenoxy)pyridin-2-yl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine - 261957 1.14.11.29 N-(4-hydroxy-1-[[6-(4-methylphenoxy)pyridin-3-yl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine - 261958 1.14.11.29 N-(methoxyoxoacetyl)-glycine methyl ester a pan-hydroxylase inhibitor, in vitro and in vivo inhibition 89458 1.14.11.29 N-([1,1'-biphenyl]-4-yl)-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide compound stabilizes HIF-1alpha levels 261986 1.14.11.29 N-benzyl-2-[2-(3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamide - 220888 1.14.11.29 N-benzyl-2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamide - 220891 1.14.11.29 N-oxalyl-(2S)-alanine competed by 2-oxoglutarate, no inhibition by the enantiomer N-oxalyl-(2R)-alanine 151045 1.14.11.29 N-oxalylglycine competed by 2-oxoglutarate 9586 1.14.11.29 N-oxalylglycine - 9586 1.14.11.29 N-[(1,3-dihydro-2-benzofuran-5-yl)methyl]-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide - 261996 1.14.11.29 N-[(3,4-dimethoxyphenyl)(8-hydroxyquinolin-7-yl)methyl]-2-phenylacetamide optimized adaptaquin analog, shows no toxicity up to a 100fold increased range over EC50. The drug is ismetabolized by CYP3A4 and CYP2B6 262005 1.14.11.29 N-[([1,1'-biphenyl]-4-yl)methyl]-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide - 262010 1.14.11.29 N-[1-[([1,1'-biphenyl]-4-yl)methyl]-4-hydroxy-2-oxo-1-azaspiro[5.5]undec-3-ene-3-carbonyl]glycine lead compound for synthesis of orally administered agents for the treatment of renal anemia 262011 1.14.11.29 oxalylglycine - 2304 1.14.11.29 oxygen the transiently overexpressed HPH-1 enzyme is inhibited by a low-oxygen environment 1180 1.14.11.29 PN-3602 - 220883 1.14.11.29 Pyridine-2,4-dicarboxylate - 1935 1.14.11.29 RuCl3 inhibitor of PHD2 under the standard assay conditions in presence of 10 microM Fe(II). This effect can be alleviated by supplementing the enzymatic reaction mixture with excess Fe(II) 94928 1.14.11.29 tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate potent and selective inhibitor of isoform PHD2 220870 1.14.11.29 TM6008 - 220877 1.14.11.29 TM6089 - 220878 1.14.11.29 Zn2+ - 14 1.14.11.29 [(1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid - 220868 1.14.11.29 [(1-chloro-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid - 220867 1.14.11.29 [(2E)-3-hydroxy-2-({[(naphthalen-2-yl)methanesulfonyl]acetyl}imino)-2,3-dihydro-1,3-thiazol-4-yl]acetic acid - 220869 1.14.11.29 [(4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid - 220866 1.14.11.29 [2-(3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetic acid - 220887 1.14.11.29 [2-(3-hydroxypyridin-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl]acetic acid - 220886 1.14.11.29 [2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetic acid - 220890 1.14.11.29 [2-(5-cyano-3-hydroxypyridin-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl]acetic acid - 220889 1.14.11.29 [2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido]acetic acid - 220892