JNJ-42041935

JNJ-42041935 is a potent, competitive and selective inhibitor of prolyl hydroxylase PHD; inhibits PHD1, PHD2, and PHD3 with pK_i values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively. IC50 & Target: pK_i: 7.91±0.04 (PHD1), 7.29 ±0.05 (PHD2), 7.65±0.09(PHD3)^[1] In Vitro: JNJ-42041935 is the most potent inhibitor of PHD2_181–417 with a pIC₅₀ value of 7.0±0.03. JNJ-42041935 also inhibits full-length PHD1, PHD2, and PHD3 enzymes (pK_i values 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively) ^[1]. In Vivo: JNJ-42041935 is 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) is effective in reversing inflammation induced anemia, whereas erythropoietin has no effect. Administration of JNJ-42041935 (100 μmol/kg p.o.) for 5 consecutive days resulted in a 2-fold increase in reticulocytes, an increase in hemoglobin by 2.3 g/dl, and an increase in the hematocrit of 9%. Two hours after oral administration of 300 μmol/kg JNJ-42041935, the bioluminescence over the peritoneal area is increased by 2.2 ± 0.3-fold relative to luciferase-treated vehicle controls in the mouse ^[1].