JNJ-42041935

Description	in vitro: JNJ-42041935 was the most potent inhibitor of PHD2181–417 with a pIC50 value of 7.0 ± 0.03. JNJ-42041935 also inhibited full-length PHD1, PHD2, and PHD3 enzymes (pKI values = 7.91 ± 0.04, 7.29 ± 0.05, and 7.65 ± 0.09, respectively). JNJ-42041935 was highly selective for PHD relative to FIH (pIC50~4). JNJ-42041935 and desferrioxamine were approximately equipotent in the HIF-1α accumulation and erythropoietin secretion assays in Hep3B cells . in vivo: 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 was increased by 2.2 ± 0.3-fold relative to luciferase-treated vehicle controls in the mouse .
Pathways	Angiogenesis/Protein Tyrosine Kinase
Targets	HIF

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