BMS 986094
Names
Biological Activity
[Description]:
BMS-986094 is a potent inhibitor of hepatitis C virus (HCV) replication, with an EC50 of 35 nM at 24 h in Huh-7 cells. BMS-986094 is a phosphoramidate prodrug of 6-O-methyl-2’-C-methyl guanosine, and can be researched for chronic HCV infection[1][2].
[Related Catalog]:
[Target]
EC50: 35 nM (HCV)[1]
[In Vitro]
BMS-986094 (INX-08189) is a highly potent inhibitor of HCV replication, with the EC50s of 10 nM against genotype 1b, 12 nM against genotype 1a, and 0.9 nM against genotype 2a after 72 h of exposure. And the concentration resulting in 50% cellular cytotoxicity (CC50) in cultured Huh-7 cells is 7.01 μM[1]. BMS-986094 (5-80 nM; 14 days) decreases luciferase activity in a concentration-dependent manner in genotype 1b replicon cells[1]. BMS-986094 (20 μM; 3 days ) decreases relative mitochondrial copy number of 11% in CEM cells. BMS-986094 (1 μM; 14 days ) has no effect on mitochondrial copy number in CEM cells. BMS-986094 does not alter the relative mitochondrial copy number in HepG2 cells[1]. MS-986094 (10 µM; 24 hours) does not increase apparently in the concentration of BMS-986094 or its metabolites in human hepatocytes (HHs) and human cardiomyocytes (HCMs) except that intracellular concentrations of INX-09114 increases and plateaues after a 7-hour incubation in HCM[3].
[In Vivo]
BMS-986094 (3-300 mg/kg; p.o.) converts to 2′-C-Me-GTP after oral administration, and 2’-C-MeG in the plasma is proportional to the production of 2’-C-MeGTP in the liver[1]. BMS-986094 (25 mg/kg; p.o.) is efficiently extracts from the portal circulation by the liver following oral administration in cynomolgus monkeys[1]. BMS-986094 (15 or 30 mg/kg/d; p.o. for 3 weeks) administers cynomolgus monkeys, the nucleoside metabolite M2 was the major plasma analyte, and INX-09114 was the highest drug-related species in the heart and kidney[3]. Animal Model: Male Sprague-Dawley rats[1] Dosage: 3, 5, 10, 25 mg/kg Administration: A single p.o. administration Result: At doses of ≥5 mg/kg, the concentrations of 2′-C-MeGTP in the liver exceeded the EC90 soon after dosing and remained at or above this level for 72 h.
[References]
Chemical & Physical Properties
[ Density]:
1.47
[ Molecular Formula ]:
C30H39N6O9P
[ Molecular Weight ]:
658.63900
[ Exact Mass ]:
658.25200
[ PSA ]:
212.94000
[ LogP ]:
3.67170