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Abstract
Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib.
Acknowledgments
This research was supported in part by the Washington University Institute of Clinical and Translational Sciences grant (UL1TR000448), the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), the National Cancer Institute of the NIH under Award Number U54CA199092, and the Multiple Myeloma Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official view of the funding agencies.
Disclosure
Abdel Kareem Azab reports receiving commercial research grant from Selexys, Verastem, Karyopharm, and Cellworks and is the founder and owner of Targeted Therapeutics LLC and Cellatrix LLC. The other authors report no conflicts of interest in this work.