tcsc0672 Tegobuvir

Tegobuvir is a specific, covalent inhibitor of the HCV NS5B polymerase.

In Vitro: Tegobuvir rapidly increases the proportion of replicons with the Y448H mutation in a dose-dependent manner. After 3 days of treatment, 1.2%, 6.8%, and > 50% of the replicon population expresses Y448H with the use of Tegobuvir at 1, 10, and 20 times its 50% effective concentration, respectively^[1]. Tegobuvir exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with Tegobuvir results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel^[2]. Tegobuvir is potent in GT1a and 1b with mean EC₅₀s of 19.8 and 1.5 nM respectively. For genotype 3a, 4a, and 6a Con chimeras, tegobuvir EC₅₀s are all greater than 100 nM. The F445C NS5B mutations in GT3a, 4a, and 6a chimeric replicons restore tegobuvir potency to EC₅₀ levels comparable to GT1a^[3].