PF-07321332

PF-07321332 is an orally bioavailable inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro), also known as 3C-like protease (3CL^pro), with a K_i value of 3.11 nM.¹ It also inhibits M^pro from other members of the Betacoronavirus genus, including SARS-CoV-1, HKU1-CoV, OC43-CoV, and MERS-CoV (K_is = 4.94, 189, 36.4, and 187 nM, respectively), as well as M^pro from NL-63-CoV and 229E CoV (K_is = 226 and 44.4 nM, respectively), which are members of the Alphacoronavirus genus. PF-07321332 is selective for these enzymes over several other proteases, including human and HIV-1 proteases (IC₅₀s = >100 µM for all), as well as a panel of G protein-coupled receptors, kinases, and transporters (IC₅₀s = ≥100 µM for all). It inhibits SARS-CoV-2 replication in A549 cells (EC₅₀ = 77.9 nM) and reduces the cytopathic effect of SARS-CoV-2 in infected Vero E6 cells (EC₅₀ = 74.5 nM) with a 50% cytotoxic concentration (CC₅₀) value of greater than 100 µM. PF-07321332 (300 and 1,000 mg/kg) reduces lung viral titers and the severity of pulmonary lesions in mice infected with the mouse-adapted SARS-CoV-2 MA10 variant. Formulations containing PF-07321332 have been used in the treatment of COVID-19.

WARNING This product is not for human or veterinary use.

1. Owen, D.R., Allerton, C.M.N., Anderson, A.S., et al. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Science 374(6575), 1586-1593 (2021).