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Daclatasvir-d6 is intended for use as an internal standard for the quantification of daclatasvir by GC- or LC-MS. Daclatasvir is a first generation direct-acting inhibitor of hepatitis C virus (HCV) non-structural protein 5A (NS5A; Kds = 8 and 210 nM for the NS5A33-202 and NS5A26-202 residues of HCV genotype 1b, respectively).1,2 It potently inhibits HCV replication in multiple HCV replicon genotypes (EC50s = 9-146 pM) with the highest potency in genotypes 1b and 4a (EC50s = 9 and 12 pM, respectively).1 Daclatasvir disrupts the subcellular localization of NS5A in Huh7.5 cells and inhibits viral RNA synthesis and virion assembly and secretion when used at a concentration of 1 nM in HCV-infected Huh7 cells.3,4 Daclatasvir also inhibits organic anion transport polypeptides 1B1 (OAT1B1) and OAT1B3 (IC50s = 1.5 and 3.27 μM, respectively).5 Formulations containing daclatasvir have been used alone and in combination with NS3/4A and NS5B inhibitors in the treatment of HCV.

|1. Gao, M., Nettles, R.E., Belema, M., et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465(7294), 96-100 (2010).|2. Ascher, D.B., Wielens, J., Nero, T.L., et al. Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA. Sci. Rep. 4, 4765 (2014).|3. Lee, C., Ma, H., Hang, J.Q., et al. The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein. Virology 414(1), 10-18 (2011).|4. Guedj, J., Dahari, H., Rong, L., et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc. Nat. Acad. Sci. USA 110(10), 3991-3996 (2013).|5. Furihata, T., Matsumoto, S., Fu, Z., et al. Different interaction profiles of direct-acting anti-hepatitis C virus agents with human organic anion transporting polypeptides. Antimicrob. Agents Chemother. 58(8), 4555-4565 (2014)..
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