BMS-929075 is a potent and orally active HCV NS5B replicase palm site allosteric inhibitor. BMS-929075 shows high oral bioavailability. BMS-929075 shows cytotoxicity.
Rats, 2 mg/kg i.v.; 6 mg/kg p.o.[1].
BMS-929075 (0-60 µM) shows cytotoxicity with CC50 values of 60, >12.5, >50 µM for Huh-7, HepG2, primary human hepatocytes, respectively[1].
BMS-929075 (compound 37) (2 mg/kg for i.v.; 6 mg/kg for p.o.) shows good pharmacokinetic parameters with oral bioavailability of 48% in rats[1].
Pharmacokinetic Parameters of BMS-929075 in Male Sprague-Dawley rats[1].
| IV | PO | |||||||||
| species | Cl (mL/min/kg) | IV t1/2(hr) | Vss(L/kg) | Cmax(µM) | Tmax(hr) | AUC (µM h) | C6 liver (µM) | C24 liver (µM) | C24 liver/plasma (µM) | F% (mL/min/kg) |
| rat | 1.7 | 4.7 | 0.7 | 7.5 | 4 | 54.5 | 15.1 | 1.12 | 1.6 | 48 |
References:
[1]. Yeung KS, et al. Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor (BMS-929075) Advanced to Phase 1 Clinical Studies. J Med Chem. 2017 May 25;60(10):4369-4385.