%0 Journal Article %A Terrance D Barrett %A Heather L Palomino %A Theresa I Theresa I. Brondstetter %A Kimon C Kanelakis %A Xiaodong Wu %A Peter V Haug %A Wen Yan %A Andy Young %A Hong Hua %A Juliet C Hart %A Da-Thao Tran %A Hariharan Venkatesan %A Mark D Rosen %A Hillary M Peltier %A Kia Sepassi %A Michele C Rizzolio %A Scott D Bembenek %A Tara Mirzadegan %A Michael H Rabinowitz %A Nigel P Shankley %T Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective HIF prolyl hydroxylase (PHD) inhibitor %D 2011 %R 10.1124/mol.110.070508 %J Molecular Pharmacology %P mol.110.070508 %X The HIF prolyl hydroxylase (PHD) enzymes represent novel targets for the treatment of anemia, ulcerative colitis, ischemic and metabolic disease inter alia. We have identified a novel small molecule inhibitor of PHD (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 to other compounds described in the literature as PHD inhibitors. JNJ-42041935, was a potent (pKI=7.3 to 7.9), 2-oxoglutarate competitive, reversible and selective inhibitor of PHD enzymes. In addition, JNJ-42401935 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. %U https://molpharm.aspetjournals.org/content/molpharm/early/2011/03/03/mol.110.070508.full.pdf