For research use only. Not for therapeutic Use.
JNJ-42041935(CAT: I000701) is a potent and selective inhibitor of PHD (prolyl hydroxylase domain) enzymes. It competes with 2-oxoglutarate and reversibly inhibits the activity of PHD enzymes. PHD enzymes are involved in the regulation of cellular responses to hypoxia, and inhibiting their activity can have potential therapeutic implications, particularly in conditions such as cancer and ischemic diseases.
| Catalog Number | I000701 |
| CAS Number | 1193383-09-3 |
| Synonyms | HIF-PHD Inhibitor II |
| Molecular Formula | C₁₂H₆ClF₃N₄O₃ |
| Purity | ≥95% |
| Target | HIF/HIF Prolyl-Hydroxylase |
| Solubility | DMSO: ≥ 36 mg/mL |
| Storage | -20°C |
| InChI | 1S/C12H6ClF3N4O3/c13-6-1-7-8(2-9(6)23-12(14,15)16)19-11(18-7)20-4-5(3-17-20)10(21)22/h1-4H,(H,18,19)(H,21,22) |
| InChIKey | FXHHASJVTYRJHH-UHFFFAOYSA-N |
| SMILES | C1=C2C(=CC(=C1Cl)OC(F)(F)F)N=C(N2)N3C=C(C=N3)C(=O)O |
| Reference | 1:Mol Pharmacol. 2011 Jun;79(6):910-20. doi: 10.1124/mol.110.070508. Epub 2011 Mar 3. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor.Barrett TD,Palomino HL,Brondstetter TI,Kanelakis KC,Wu X,Haug PV,Yan W,Young A,Hua H,Hart JC,Tran DT,Venkatesan H,Rosen MD,Peltier HM,Sepassi K,Rizzolio MC,Bembenek SD,Mirzadegan T,Rabinowitz MH,Shankley NP, PMID: 21372172 DOI: 10.1124/mol.110.070508 </br><span>Abstract:</span> The hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) enzymes represent novel targets for the treatment of anemia, ulcerative colitis, and ischemic and metabolic disease inter alia. We have identified a novel small-molecule inhibitor of PHD, 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), through structure-based drug design methods. The pharmacology of JNJ-42041935 was investigated in enzyme, cellular, and whole-animal systems and was compared with other compounds described in the literature as PHD inhibitors. JNJ-42041935, was a potent (pK(I) = 7.3-7.9), 2-oxoglutarate competitive, reversible, and selective inhibitor of PHD enzymes. In addition, JNJ-42041935 was used to compare the effect of selective inhibition of PHD to intermittent, high doses (50 μg/kg i.p.) of an exogenous erythropoietin receptor agonist in an inflammation-induced anemia model in rats. JNJ-42041935 (100 μmol/kg, once a day for 14 days) was effective in reversing inflammation-induced anemia, whereas erythropoietin had no effect. The results demonstrate that JNJ-42041935 is a new pharmacological tool, which can be used to investigate PHD inhibition and demonstrate that PHD inhibitors offer great promise for the treatment of inflammation-induced anemia. |
