Filibuvir

Filibuvir (CAS 877130-28-4) is an orally active, selective non-nucleoside inhibitor of the hepatitis C virus NS5B RNA-dependent RNA polymerase, developed by Pfizer and also known as PF-00868554. The compound advanced through Phase 1 and Phase 2 clinical studies, demonstrating potent antiviral activity against HCV genotype 1. Enamine offers Filibuvir as a high-purity screening sample for antiviral and virology research applications.

About Filibuvir (CAS 877130-28-4)

Filibuvir molecular formula is C₂₇H₃₅F₃N₂O₅S with a molecular weight of 560.63 g/mol. The Filibuvir molecular structure is based on a dihydropyranopyrimidine scaffold carrying a sulfonamide linker and trifluoromethyl-substituted aryl group, optimized for allosteric binding within the NS5B thumb II pocket. The compound is registered under CAS 877130-28-4 and was developed as part of Filibuvir Pfizer research programs targeting chronic HCV infection. Its physicochemical properties support oral bioavailability and adequate plasma exposure in clinical settings.

Application Filibuvir

Filibuvir is applied in research targeting HCV replication mechanisms, NS5B polymerase function, and antiviral drug resistance profiling. As a thumb II allosteric inhibitor, PF-00868554 is used to study the structural and functional consequences of NS5B conformational changes during RNA elongation. The compound serves as a reference non-nucleoside inhibitor in comparative studies with other NS5B-targeting agents and in replicon-based screening assays. Filibuvir Pfizer clinical data also make it relevant for translational HCV research and resistance mutation characterization studies involving M423 variants.

Biochemical and Physiological Actions

Filibuvir binds noncovalently in the thumb II allosteric pocket of NS5B, a site spatially distinct from the catalytic active site. This binding preferentially inhibits elongative RNA synthesis rather than initiation, potently reducing viral RNA accumulation in infected cells. PF-00868554 inhibits both genotype 1a and 1b replicons with EC₅₀ values of 59 nM for each isoform. In Phase 1b clinical studies, doses of 450 mg twice daily produced more than 2-log reductions in HCV RNA, confirming target engagement in vivo. Resistance profiling identified M423I/T/V mutations at the binding site as the primary mechanism of reduced susceptibility, providing a well-defined model for studying allosteric inhibitor resistance.

Features and Benefits Filibuvir

Filibuvir (PF-00868554, CAS 877130-28-4) offers a clinically validated activity profile with clear advantages for antiviral research:

• selective thumb II allosteric NS5B inhibition with EC₅₀ of 59 nM against genotype 1a and 1b replicons;
• well-characterized Filibuvir molecular structure enabling resistance mutation and SAR studies;
• oral bioavailability with Phase 1 and Phase 2 clinical data available for translational reference;
• defined resistance profile (M423I/T/V) supporting mechanistic studies on allosteric inhibitor escape.

When sourced as EBC-501097, the compound is provided with analytical quality control data for consistent use in biochemical and cell-based antiviral assays.