MK8617 是一种口服具有活力的低氧诱导因子脯氨酰羟化酶 1-3 (HIF PHD1-3) 泛抑制剂，对于PHD2的IC50=1 nM。

MK-8617 is an orally available HIF PHD1 3 pan-inhibitor, inhibiting PHD1/2/3 (IC50: 1.0/1.0/14 nM).

In vitro, MK-8617 hasn't markedly inhibitory for CYP1A2, 3A4, 2B6, 2C9, 2C19, or 2D6 (IC50>60 μM), and is a moderate reversible inhibitor of CYP2C8 (IC50: 1.6 μM). MK-8617 (10 μM) is inactive against a general panel of 171 radioligand binding and enzymatic assays.

In liver microsomes (+NADPH) from rat, dog, and monkey, tritiated MK-8617 exhibits minimal metabolic turnover (<10%), but the significant turnover (34%) in HLMs after 60 min (10 μM compound, 1 mg/mL microsomal protein). MK-8617 has good oral bioavailability across species (36?71%), with low clearance and volume of distribution. Increases in circulating reticulocytes are observed at 5 and 15 mg/kg 3 days after challenge and at the 15 mg/kg 4 days after challenge.

1187990-87-9

C24H21N5O4

443.463

MK8617

DMSO:16 mg/mL (36.1 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years