BMS-986094  (Synonyms: INX-08189)

BMS-986094 (INX-08189) 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 proagent of 6-O-methyl-2’-C-methyl guanosine. BMS-986094 can be used for the research of chronic HCV infection^[1][2].

EC50: 35 nM (HCV)^[1]

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

658.64

Solid

C₃₀H₃₉N₆O₉P

1234490-83-5

C[C@]([C@](O[C@@H]1CO[P](OC2=CC=CC3=C2C=CC=C3)(N[C@@H](C)C(OCC(C)(C)C)=O)=O)([H])N4C5=NC(N)=NC(OC)=C5N=C4)([C@@H]1O)O

Room temperature in continental US; may vary elsewhere.

• [1]. Vernachio JH, et, al. INX-08189, a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob Agents Chemother. 2011 May; 55(5): 1843-51.  [Content Brief]

  [2]. McGuigan C, et, al. Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus. Bioorg Med Chem Lett. 2010 Aug 15; 20(16): 4850-4.  [Content Brief]

  [3]. Li W, et, al. In Vitro Metabolite Formation in Human Hepatocytes and Cardiomyocytes and Metabolism and Tissue Distribution in Monkeys of the 2'-C-Methylguanosine Prodrug BMS-986094. Int J Toxicol. 2017 Jan 1; 1091581816683642.  [Content Brief]