Screening small molecular inhibitors of STAT3 based on surface plasmon resonance technology
10.12206/j.issn.1006-0111.202105137
- VernacularTitle:基于表面等离子体共振技术筛选STAT3小分子抑制剂的研究
- Author:
Xiaowei SU
1
;
Hualin ZHANG
2
;
Ning ZHANG
3
;
Ben YANG
3
;
Weiheng XU
3
;
Junping ZHANG
1
Author Information
1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China.
2. The 81st Army Hospital, Zhangjiakou 075001, China.
3. School of Pharmacy, Naval Medical University, Shanghai 200433, China.
- Keywords:
surface plasmon resonance;
STAT3;
small molecular inhibitors;
apigenin
- From:
Journal of Pharmaceutical Practice
2021;39(6):515-519
- CountryChina
- Language:Chinese
-
Abstract:
Objective To find small molecules binding specifically to signal transducer and activator of transcription3 (STAT3) based on surface plasmon resonance (SPR) technology and confirm their inhibitory activities to STAT3. Methods The biomolecular interaction analysis T200 system based on SPR technology was used to couple the purified protein STAT3 to CM5 chip under the optimal pH conditions. The compounds with high binding response value were screened out from 50 candidate compounds derived from traditional Chinese medicines and the binding specificity was then confirmed. Biological experiments were performed to confirm the inhibitory effects of the screened compounds on STAT3. The binding pattern of STAT3 and the compound was fitted by molecular docking technique. Results More than 10 candidate molecules exhibited binding activities to STAT3 and kinetics assays revealed that only one candidate molecule, apigenin, showed specific binding. Western-blot analysis exhibited that apigenin inhibited the phosphorylation of STAT3 dose-dependently. Luciferase reporter gene assays demonstrated that apigenin also inhibited IL-6-induced STAT3 transcriptional activity in a dose-dependent manner. Molecular docking results showed that apigenin binds to the SH2 domain of STAT3, and interacts with key residues Glu638, Gln644, Gly656 and Lys658 by hydrogen bonds and with Tyr657 through π-π interactions. Conclusion Apigenin was a direct inhibitor of STAT3.
