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Mcl-1抑制:应对多发性骨髓瘤中的恶性肿瘤

Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma.

作者信息

Al-Odat Omar, von Suskil Max, Chitren Robert, Elbezanti Weam, Srivastava Sandeep, Budak-Alpddogan Tulin, Jonnalagadda Subash, Aggarwal Bharat, Pandey Manoj

机构信息

Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, United States.

Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ, United States.

出版信息

Front Pharmacol. 2021 Jul 19;12:699629. doi: 10.3389/fphar.2021.699629. eCollection 2021.

Abstract

Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and could be used as single agent or combined with existing therapies.

摘要

多发性骨髓瘤(MM)是一种浆细胞肿瘤。Bcl-2家族蛋白的过表达,尤其是髓样细胞白血病1(Mcl-1),在MM的发病机制中起关键作用。Mcl-1的过表达与MM的耐药性及总体不良预后相关。因此,抑制Mcl-1蛋白被认为是一种杀死骨髓瘤细胞的治疗策略。在过去十年中,选择性Mcl-1抑制剂的研发取得了显著进展。本综述介绍了Mcl-1在MM进展中的关键作用,最突出的选择性抑制Mcl-1的BH3模拟物和半BH3模拟物,它们可作为单一药物或与现有疗法联合使用。

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