2. Academic Validation
  3. Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains

Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains

  • Bioorg Med Chem. 2017 Jan 1;25(1):138-152. doi: 10.1016/j.bmc.2016.10.020.
Yichao Wan 1,  Tingting Liu 1,  Xiaoxian Li 1,  Chen Chen 1,  Hao Fang 2
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
  • 2 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China. Electronic address: haofangcn@sdu.edu.cn.
PMID: 27810438 DOI: 10.1016/j.bmc.2016.10.020
Abstract

As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for Cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki=0.077μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki=0.18μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki=8.45μM), which was the same as positive control Gossypol (Ki=7.54μM).

Keywords

Bcl-2; Cancer; Mcl-1; Pyrrolidine; Target.

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