Discovery of bepridil as a valuable lead compound with potent p53-MDM2 inhibitory activity
10.12206/j.issn.1006-0111.202009031
- VernacularTitle:小分子p53-MDM2抑制剂先导化合物苄普地尔的研究
- Author:
Chuan LUO
1
;
Jing LI
2
;
Wannian ZHANG
2
;
Zhenyuan MIAO
2
Author Information
1. Anhui Huarun Golden Frog Pharmaceutical Co., Ltd., Huaibei 235000, China.
2. School of Pharmacy, Naval Medical University, Shanghai 200433, China.
- Keywords:
new uses of old drugs strategy;
drug design;
bepridil;
p53-MDM2 inhibitor
- From:
Journal of Pharmaceutical Practice
2021;39(2):126-129
- CountryChina
- Language:Chinese
-
Abstract:
Objective To find novel lead compounds as p53-MDM2 inhibitors by drug repurposing strategy. Methods The p53-MDM2 inhibitory activities of compounds were determined by FP and western blotting. MTT method was used to determine the in-vitro antitumor activities. The metabolites in human liver microsomes were tested. Results Bepridil showed excellent in-vitro anti-tumor activity and strong p53-MDM2 protein binding inhibitory activity, which can significantly reduce the expression of MDM2 protein in a dose-dependent manner. The metabolites in human liver microsomes are mainly benzene ring hydroxyl mono-oxidation metabolites. Conclusion Bepridil can be used as a lead compound for p53-MDM2 protein binding small molecule inhibitors for subsequent structural optimization design studies.
