Target Validation Information
TTD ID	T05152
Target Name	Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B)
Type of Target	Successful
Drug Potency against Target	HCV-796	Drug Info	IC50 = 17 nM	[1]
	R7128	Drug Info	IC50 = 610 nM	[1]
	A-837093	Drug Info	EC50 = 6 nM	[2]
Action against Disease Model	HCV-796	Drug Info	HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric h uMan livers, and in h uMans infected with hepatitis C virus.. Enzyme assays yielded median inhibitory concentration (IC(50)) values of 0.01 to 0.14 microM for genotype 1, with half maximal effective concentration (EC(50)s) of 5 nM and 9 nM against genotype 1a and 1b replicons. In the chimeric mouse model, a 2.02 +/- 0.55 log reduction in HCV titer was seen with monotherapy, whereas a suboptimal dose of 30 mg/kg three times per day in combination with interferon demonstrated a 2.44 log reduction (P = 0.001 versus interferon alone)	[3]
References
REF 1	Recent progress in the development of selected hepatitis C virus NS3.4A protease and NS5B polymerase inhibitors. Curr Opin Pharmacol. 2008 Oct;8(5):522-31.
REF 2	The exploding field of the HCV polymerase non-nucleoside inhibitors: summary of a first generation compounds. Mini Rev Med Chem. 2008 Oct;8(12):1298-310.
REF 3	HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology. 2009 Mar;49(3):745-52.

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