Carfilzomib

Carfilzomib is a second-generation, irreversible, peptide epoxyketone class proteasome inhibitor that targets the chymotrypsin-like β5 subunit of the constitutive 20S proteasome (IC₅₀ = 5.2 nM) and the β5i subunit of the immunoproteasome 20Si (LMP7; IC₅₀ = 14 nM) with minimal cross reactivity to other proteases.^1,2 It can induce cell cycle arrest and apoptosis in human cancer cell lines including multiple myeloma, lymphoma, and various solid tumors (IC₅₀s = 2.4-20 nM).^3,4

WARNING This product is not for human or veterinary use.

1. Dou, Q.P., and Zonder, J.A. Overview of proteasome inhibitor-based anti-cancer therapies: Perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system. Curr. Cancer Drug Targets 14(6), 517-536 (2014).

2. Zhou, H.J., Aujay, M.A., Bennett, M.K., et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J. Med. Chem. 52(9), 3028-3038 (2009).

3. Zhang, W., and Sidhu, S.S. Development of inhibitors in the ubiquitination cascade. FEBS Lett. 588(2), 356-367 (2014).

4. Demo, S.D., Kirk, C.J., Aujay, M.A., et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 67(13), 6383-6391 (2007).

Chen, Y., Lear, T.B., Evankovich, J.W., et al. A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry. Nat. Commun. 12(1), 3907 (2021).

Zerfas, B.L., Maresh, M.E., and Trader, D.J. The immunoproteasome: An emerging target in cancer and autoimmune and neurological disorders. J. Med. Chem. (2019).