2130-96-3Relevant articles and documents
Discovery and development of substituted tyrosine derivatives as Bcl-2/Mcl-1 inhibitors
Liu, Renshuai,Liu, Lulu,Liu, Tingting,Yang, Xinying,Wan, Yichao,Fang, Hao
, p. 4907 - 4915 (2018)
Anti-apoptotic Bcl-2 family proteins are vital for cancer cells to escape apoptosis, which make them attractive targets for cancer therapy. Recently, a lead compound 1 was found to modestly inhibit the binding of BH3 peptide to Bcl-2 protein with a Ki value of 5.2 μM. Based on this, a series of substituted tyrosine derivatives were developed and tested for their binding affinities to Bcl-2 protein. Results indicated that these compounds exhibited potent binding affinities to Bcl-2 and Mcl-1 protein but not to Bcl-XL protein. Promisingly, compound 6i inhibited the binding of BH3 peptide to Bcl-2 and Mcl-1 protein with a Ki value of 450 and 190 nM respectively, and showed obvious anti-proliferative activities against tested cancer cells.
Design, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors
Chen, Chen,Nie, Yiming,Xu, Guangsen,Yang, Xinying,Fang, Hao,Hou, Xuben
, p. 2771 - 2783 (2019/05/15)
Bcl-2 family proteins, which divides into pro-apoptosis proteins and anti-apoptosis proteins, are involved in cell apoptosis progression. As numerous studies illustrated, targeting Bcl-2 family proteins is more and more attractive and practicable to cancer treatment. In this work, we designed and synthesized a series of indomethacin derivatives as new inhibitors for Bcl-2 family proteins. Our results of binding assay to Bcl-2 proteins, MTT assay and apoptotic assay indicated that some compounds had potent binding affinity to Bcl-2/Mcl-1 but not Bcl-XL. Furthermore, compound 8j showed improved anti-proliferative activity than known Bcl-2 inhibitor WL-276.
Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
Wan, Yichao,Liu, Tingting,Li, Xiaoxian,Chen, Chen,Fang, Hao
, p. 138 - 152 (2016/12/22)
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= 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki= 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki= 8.45 μM), which was the same as positive control Gossypol (Ki= 7.54 μM).