Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice
AbstractMultiple myeloma (MM) is the most common cancer affecting the bone and bone marrow and remains incurable for most patients; novel therapies are therefore needed. Bortezomib (Btz) is an FDA-approved drug for the treatment of patients with MM. However, its severe side effects require a dose reduction or the potential discontinuation of treatment. To overcome this limitation, we conjugated Btz to a bisphosphonate (BP) residue lacking anti-osteoclastic activity using a novel chemical linker and generated a new bone-targeted Btz-based (BP-Btz) proteasome inhibitor. We demonstrated that BP-Btz, but not Btz, bound to bone slices and inhibited the growth of MM cells in vitro. In a mouse model of MM, BP-Btz more effectively reduced tumor burden and bone loss with less systemic side effects than Btz. Thus, BP-Btz may represent a novel therapeutic approach to treat patients with MM. View Full-Text
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Wang, H.; Xiao, L.; Tao, J.; Srinivasan, V.; Boyce, B.F.; Ebetino, F.H.; Oyajobi, B.O.; Boeckman, R.K., Jr.; Xing, L. Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice. Pharmaceutics 2018, 10, 154.
Wang H, Xiao L, Tao J, Srinivasan V, Boyce BF, Ebetino FH, Oyajobi BO, Boeckman RK, Jr, Xing L. Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice. Pharmaceutics. 2018; 10(3):154.Chicago/Turabian Style
Wang, Hua; Xiao, Lifeng; Tao, Jianguo; Srinivasan, Venkat; Boyce, Brendan F.; Ebetino, Frank H.; Oyajobi, Babatunde O.; Boeckman, Robert K., Jr.; Xing, Lianping. 2018. "Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice." Pharmaceutics 10, no. 3: 154.
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