Identification of a Novel Bcl-2 Inhibitor by Ligand-Based Screening and Investigation of Its Anti-cancer Effect on Human Breast Cancer Cells

Conclusions In this study, a virtual screening process including RF classification and regression models was applied to identify the novel Bcl-2 inhibitors. We finally screened out the compound M1 as a novel Bcl-2 small molecule inhibitor, which binds to and down-regulates Bcl-2, has significant cytotoxic effect by inducing mitochondria-mediated apoptosis. Compound M1 could be a novel and promising hit or lead compound for further structural optimization in drug discovery. Ethics Statement We have explored the anti-tumor effect of Compound M1 in vitro. The human breast cancer cell lines MDA-MB-231, T47D, and BT549, were purchased from Cell Bank of Chinese Academy of Sciences. Author Contributions YC and DC designed, conceived the study, and revised the manuscript. MW, ZD, SJ, YG, and HW performed the experiments and analyzed data. MW and ZD drafted the manuscript. XW, SX, YZ, and JY provided technical support in the experiments. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments This work was supported by grants from the National Natural Science Foundation of China No. 81422051, 81402853 and 81472593, the National Key Basic Research Program (2015CB910700), the Project of Innovation-driven Plan in Central South University (502211812), and the Hunan Natural Science Foundation of China No. 2016JJ1020. Th...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research