Myeloid cell leukemin-1 inhibitors: a growing arsenal for cancer therapy
Myeloid cell leukemin-1 inhibitors: a growing arsenal for cancer therapy
复制标题
骨髓细胞 leukemin-1 抑制剂：不断增长的癌症治疗武器库
DOI：
10.1016/j.drudis.2020.07.021
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发表时间：
2020
影响因子：
7.4
通讯作者：
Jiang Zheng-Yu
中科院分区：
文献类型：
--
作者：
Zhu Peng-Ju;Yu Ze-Zhou;You Qi-Dong;Jiang Zheng-Yu
HighlightsMcl-1 inhibition is a promising way for cancer therapy.Drug resistance and side effects of Bcl-2 inhibitors are obvious in clinical trials.Binding mode between Bim BH3 peptide and Mcl-1 provides a point for designing Mcl-1 inhibitors.Cocrystal structures of compounds bound to Mcl-1 guide development of Mcl-1 inhibitors.B-cell lymphoma-2 (Bcl-2) family proteins, comprising proapoptotic proteins (Bax and Bak), antiapoptotic proteins (Bcl-2, Bcl-X L, Bcl-w, Mcl-1, and A1) and BCL-2 homology domain 3 (BH3)-only proteins (Bid, Noxa, and Puma), have long been identified as pivotal apoptosis regulators. As an antiapoptotic member, myeloid cell leukemin-1 (Mcl-1) can bind with proapoptotic proteins and inhibit apoptosis. Mcl-1 is frequently overexpressed and closely associated with oncogenesis and poor prognosis in several cancers, posing a tremendous obstacle for cancer therapy. Recently, an increasing number of Mcl-1-selective small-molecule inhibitors have entered preclinical studies and advanced into clinical trials. In this review, we briefly introduce the role of Mcl-1 in apoptosis and highlight the recent development of Mcl-1 small-molecule inhibitors.
