Screening small molecular inhibitors of STAT3 based on surface plasmon resonance technology / 药学实践杂志

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.

Research progress of protein arginine methyltransferase 5 inhibitors / 中国药科大学学报

@#Protein arginine methyltransferases, which proceed the post-translational modification of both histones and non-histones, play an important role in many biological pathways. Protein arginine methyltransferase 5 (PRMT5) is a major enzyme responsible for symmetric di-methylation of arginine residues and has been suggested as a potential therapeutic target for tumors.In the past decade,the discovery and development of PRMT5 inhibitors have become one of the most important research fields.This article introduces the structure and biochemical function of PRMT5 and its correlation with cancer reviews, the binding modes and biological data of PRMT5 inhibitors under development, and discusses the clinical application potential of PRMT5 inhibitors in the treatment of cancer.

Advances in BET bromodomain protein inhibitors / 中国药科大学学报

@#Recognizing acetyl-lysine of histone is a key process of epigenetic regulation that is mediated by a protein module called bromodomain(BRD). The bromodomain inhibitors of the bromodomains and extra-terminal(BET)family have shown great potential in anti-inflammatory and antiproliferative effects. Through a review of diseases and structures about BET bromodomain, different kinds of inhibitors were analyzed and their structure-activity relationships were summarized. Herenin, the recent advances reported are reviewed for discovering more excellent small molecule inhibitors.