41044-80-8Relevant academic research and scientific papers
Synthesis of a bone-targeted bortezomib with in vivo anti-myeloma effects in mice
Wang, Hua,Xiao, Lifeng,Tao, Jianguo,Srinivasan, Venkat,Boyce, Brendan F.,Ebetino, Frank H.,Oyajobi, Babatunde O.,Boeckman, Robert K.,Xing, Lianping
, (2018)
Multiple 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.
BORTEZOMIB CONJUGATES AND METHODS USING SAME
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Page/Page column 83, (2017/06/20)
The present invention provides compositions and methods for providing controllable local delivery of a conjugate of bortezomib (Btz) and a bisphosphonate to promote bone formation. In certain embodiments, the invention is used as a treatment for a subject with diseases and disorders characterized by bone loss.
