HIF-PHD Inhibitor II 是一种高效的，竞争性的、选择性的脯氨酰羟化酶PHD抑制剂，抑制PHD1(pKi= 7.91±0.04)，PHD2 (pKi= 7.29 ±0.05) 和 PHD3 (pKi= 7.65±0.09)。

JNJ-42041935 is a potent (pKi = 7.3-7.9), 2-oxoglutarate competitive, reversible, and selective inhibitor of PHD enzymes.

JNJ-42041935 is the most potent inhibitor of PHD2181–417 with a pIC50 value of 7.0±0.03. JNJ-42041935 also inhibits full-length PHD1, PHD2, and PHD3 enzymes (pKi values 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively) [1].

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 while 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].

The potency of JNJ-42041935 for inhibition of the structurally related enzyme FIH is assessed by methods similar to those described for PHD2. In brief, activity of FIH is determined using purified glutathione transferase-tagged full-length FIH amino acids 1 to 350 and a synthetic HIF-1α peptide corresponding to residues Asp788 to Leu822. Compounds are preincubated with 17.1 nM FIH for 30 min, followed by a 10-min incubation with 1 μM [2-14C]2-oxoglutarate, in the presence of 10 μM FeNH4SO4 in reaction buffer. The selectivity of JNJ-42041935 for inhibition of a range of other targets available for testing in commercial assays is also assessed at concentrations of 1 and 10 μM[1].

1193383-09-3

C12H6ClF3N4O3

346.65

HIF-PHD Inhibitor II

DMSO:36 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years