Drug intelligence / Profile preview

PF-00835231

Development stage
Preclinical
Lead developer
Pfizer
Modality
Small Molecules
Administration
Intravenous
01

Overview

PF-00835231 is a **small molecule antiviral inhibitor** targeting the coronavirus main protease (**3CL protease**, also called M^pro^), a critical enzyme required for viral replication[1][2][3][4]. By covalently and selectively inhibiting the 3CL protease, PF-00835231 blocks the processing of viral polyproteins, thereby preventing the maturation and functionality of essential viral proteins[1][3][4]. PF-00835231 is the **active metabolite** of the intravenous phosphate prodrug PF-07304814, which is rapidly converted in vivo to PF-00835231[1][3]. Computational and in vitro studies demonstrate potent inhibition of SARS-CoV-2 and other coronaviruses at nanomolar to low micromolar concentrations, with substantially reduced viral replication in human airway epithelial cell models and multiple animal models[1][2][3][4]. PF-00835231 is specific to coronaviruses and does not inhibit the replication of non-coronavirus viruses[1]. It was originally designed in response to the 2003 SARS outbreak and re-investigated during the COVID-19 pandemic, entering preclinical and early clinical development[3][4]. P-glycoprotein (MDR1, ABCB1) reduces cellular accumulation of PF-00835231 in some cell models, but does not limit effectiveness in human airway cells[1][2][3].

Other names
PF-00835231PF00835231PF 00835231
02

Targets

NS3/4A (Hepatitis C virus nonstructural protein 3/4A serine protease)Mpro (3C-like proteinase of SARS-CoV-2)PR (Progesterone receptor)

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