INX-08189

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

O-6-甲基-2-C-甲基鸟苷的氨基磷酸酯前药，HCV NS5B 聚合酶的有效抑制剂，在复制子测定中 IC50 为 10 nM。

A phosphoramidate prodrug of O-6-methyl-2-C-methyl guanosine, potent inhibitor of HCV NS5B polymerase with IC50 of 10 nM in replicon assay; inhibits viral replication with EC50 of 35 nM, inhibits mutant NS5b S282T mutant replicon with EC90 of 344 nM; orally active.HCV Infection Phase 2 Discontinued.

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.BMS-986094 (5-80 nM; 14 days) decreases luciferase activity in a concentration-dependent manner in genotype 1b replicon cells.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.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.

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.BMS-986094 (25 mg/kg; p.o.) is efficiently extracts from the portal circulation by the liver following oral administration in cynomolgus monkeys.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. Animal Model:Male Sprague-Dawley rats 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.

INX08189 | BMS-986094

Microbiology/Virology

HCV

HCV

Infection

HCV Infection

1234490-83-5

658.649

C30H39N6O9P

>98% (HPLC)

10 mM in DMSO

C[C@H](NP(OC1=C2C=CC=CC2=CC=C1)(OC[C@H]3O[C@@H](N4C=NC5=C(OC)N=C(N)N=C45)[C@](C)(O)[C@@H]3O)=O)C(OCC(C)(C)C)=O

Neopentyl ((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphoryl)-L-alaninate

(-20℃)

With Ice Pack

≥ 2 years