Proteasome inhibitor. Inhibits SARS-CoV in silico, probably through blocking the main protease, Mpro (3CLpro, Nsp5). Wang, J. ChemRxiv, Feb 21 2020, https://doi.org/10.26434/chemrxiv.11875446.v1; Laise et al. bioRxiv, May 17 2020, https://doi.org/10.1101/2020.05.12.091256
Biochemicals & reagents
1) Bennett and Kirk (2008) Development of proteasome inhibitors in oncology and autoimmune diseases; Curr. Opin. Drug Disc. Dev. 11 616 2) Hanada et al. (1992), Epoxomicin, a new antitumor agent of microbial origin; J. Antibiot. (Tokyo), 45 174 3) Demo et al. (2007) Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome; Cancer Res. 67 6383 4) Kuhn et al. (2007), Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma; Blood, 110 3281
Carfilzomib is a potent and irreversible proteasome inhibitor (1) being a synthetic analog of the microbial product epoxomcin (2). This compound compared to bortezomib displays equal potency but greater selectivity for the chymotrypsin-like activity of the proteasome and in cell culture it is more cytotoxic than bortezomib and hematologic tumor cells exhibit greater sensitivity than solid tumor cells. The treatment of cells with carfilzomib results in the accumulation of proteasome substrates and induction of cell cycle arrest and/or apoptosis (3), is effective against multiple myeloma (4) and is active in vivo.