标题：Small-molecule Mcl-1 inhibitors: Emerging anti-tumor agents
作者：Wan, Yichao; Dai, Ningning; Tang, Zilong; Fang, Hao
作者机构：[Wan, Yichao; Dai, Ningning; Tang, Zilong] Hunan Univ Sci & Technol, Hunan Prov Key Lab Controllable Preparat & Funct, Key Lab Theoret Organ Chem & Fu 更多
通讯作者地址：[Fang, H]Shandong Univ, Sch Pharm, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China.
来源：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
关键词：Bcl-2; Mcl-1; Apoptosis; Anti-tumor; Inhibitors
摘要：The anti-apoptotic members of B-cell lymphoma-2 (Bcl-2) proteins family, such as Bcl-2 and myeloid cell leukemia-1 (Mcl-1), are the key regulators of the intrinsic pathway of apoptosis and overexpressed in many tumor cells, which have been confirmed as potential drug targets for cancers. A number of Bcl-2 proteins inhibitors have been developed and conducted clinical trials, but no Mcl-1 inhibitors are presented in the clinics. In addition, Mcl-1 is an important reason for the resistance to radio- and chemo-therapies, including inhibitors that target other Bcl-2 family members. For example, the recently launched Bcl-2-selective inhibitor ABT-199 displays highly potency in the treatment of chronic lymphocytic leukemia (CLL), but it cannot induce the apoptosis controlled by Mcl-1 in some tumor cell lines. Therefore, developing potent Mcl-1 inhibitors become urgently needed in clinical therapy. This review briefly introduces the structure of Mcl-1 protein, the role in cancers and focuses on the progress of small molecule Mcl-1 inhibitors from 2012 to 2017. (C) 2018 Elsevier Masson SAS. All rights reserved.