Bortezomib-d15

Bortezomib-d₁₅ is intended for use as an internal stadard for the quantification of bortezomib by GC- or LC-MS. When stored as a lyophilized solid, bortezomib exists as in a trimeric boroxine form but exists as the free boronic acid in solution.¹ Bortezomib is a dipeptide boronic acid derivative that reversibly inhibits the 20S proteasome (K_i = 0.6 nM).² It binds the β5-subunit of the 20S proteasome and selectively inhibits chymotryptic activity.^3,4,5 Bortezomib blocks the degradation of tumor-suppressing and proapoptotic proteins to induce cell cycle arrest and apoptosis in cancer cell lines.^2,6

1.Byrn, S.R., Tishmack, P.A., Milton, M.J., et al.Analysis of two commercially available bortezomib products: differences in assay of active agent and impurity profileAAPS PharmSciTech12(2)461-467(2011) 2.Yamauchi, T., Keating, M.J., and Plunkett, W.UCN-01 (7-hydroxystaurosporine) inhibits DNA repair and increases cytotoxicity in normal lymphocytes and chronic lymphocytic leukemia lymphocytesMolecular Cancer Therapeutics1287-294(2002) 3.Lightcap, E.S., McCormack, T.A., Pien, C.S., et al.Proteasome inhibition measurements: Clinical applicationClinical Chemistry46(5)673-683(2000) 4.Adams, J.Development of the proteasome inhibitor PS-341The Oncologist79-16(2002) 5.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) 6.Richardson, P.G., Hideshima, T., and Anderson, K.C.Bortezomib (PS-341): A novel, first-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancersCancer Control10(5)361-369(2003)