GS-9256

GS-9256 is a selective HCV NS3 protease inhibitor. GS-9256 has good pharmacokinetic properties and antiviral activity[1].

Research Areas >> Infection

Signaling Pathways >> Metabolic Enzyme/Protease >> HCV Protease

GS-9256 (0.002-0.183 μM) has a mean EC50 value of 20 nM in GT1b huh-luc cells with a replicon encoding luciferase[1]. GS-9256 (3 μM) retains wild-type activity against all NS5B and NS5A inhibitor-resistant mutations tested and is metabolically stable in microsomes and hepatocytes including rodents, dogs and humans[1].

GS-9256 (1 mg/kg, i.v., 30 min) is highly bioavailable in mice (near 100%) and moderately bioavailable in rats (14%), dogs (21%) and monkeys (14%). The elimination half-life is approximately 2 hours in mice, 0.6 hours in rats, 5 hours in dogs, and 4 hours in monkeys[1]. The pharmacokinetic parameters of GS-9256(IV, 2 mg/kg mouse and 1 mg/kg rat, dog, monkey; Oral, 50 mg/kg mouse, 5 mg/kg rat and monkey, 4 mg/kg dog) - Parameters CD-1 mouse Sprague Dawley rat Beagle dog Cynomolgus monkey Intravenous CL(L/h/kg) 2.0 1.26 0.04 0.33 Vss (L/kg) 2.3 0.16 0.09 0.27 t1/2(h) 2.35 0.61 4.88 3.95 MRT(h) 1.15 0.13 2.11 0.82 Oral Tmax(h) 3.00 0.67 2.00 2.67 Cmax(nM) 11116 265 4369 604 t1/2(h) 1.31 0.53 4.22 4.42 AUC0-∞(nM*h) 58959 445 21043 2304 F(%) Complete 13.9 21 14