Carfilzomib-d8 is intended for use as an internal standard for the quantification of carfilzomib by GC- or LC-MS. Carfilzomib is an irreversible proteosome inhibitor classified as a peptide epoxyketone. It 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
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 systemCurr. Cancer Drug Targets14(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 cascadeFEBS 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 proteasomeCancer Res.67(13)6383-6391(2007)