950745-62-7Relevant academic research and scientific papers
Investigating the binding mode of reversible LSD1 inhibitors derived from stilbene derivatives by 3D-QSAR, molecular docking, and molecular dynamics simulation
Xu, Yongtao,He, Zihao,Yang, Min,Gao, Yunlong,Jin, Linfeng,Wang, Meiting,Zheng, Yichao,Lu, Xiaoyuan,Zhang, Songjie,Wang, Chang,Zhao, Zongya,Zhao, Junqiang,Gao, Qinghe,Duan, Yingchao
, (2019)
Overexpression of lysine specific demethylase 1 (LSD1) has been found in many cancers. Newanticancer drugs targeting LSD1 have been designed. The research on irreversible LSD1 inhibitors has entered the clinical stage, while the research on reversible LSD1 inhibitors has progressed slowly so far. In this study, 41 stilbene derivatives were studied as reversible inhibitors by three-dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q2 = 0.623, r2 = 0.987, r2 pred = 0.857) and comparative molecular similarity indices analysis (CoMSIA q2 = 0.728, r2 = 0.960, r2 pred = 0.899) were used to establish the model, and the structure-activity relationship of the compounds was explained by the contour maps. The binding site was predicted by two different kinds of software, and the binding modes of the compounds were further explored. A series of key amino acids Val288, Ser289, Gly314, Thr624, Lys661 were found to play a key role in the activity of the compounds. Molecular dynamics (MD) simulations were carried out for compounds 04, 17, 21, and 35, which had different activities. The reasons for the activity differences were explained by the interaction between compounds and LSD1. The binding free energy was calculated by molecular mechanics generalized Born surface area (MM/GBSA). We hope that this research will provide valuable information for the design of new reversible LSD1 inhibitors in the future.
Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors
Jung, Mankil,Lee, Yongnam,Park, Moonsoo,Kim, Hanjo,Kim, Heekyeong,Lim, Eunyoung,Tak, Jungae,Sim, Minjoo,Lee, Dongeun,Park, Namsoo,Oh, Won Keun,Hur, Kyu Yeon,Kang, Eun Seok,Lee, Hyun-Chul
, p. 4481 - 4486 (2008/02/13)
Dihydroxy stilbene derivatives were designed based on lithospermic acid B and were prepared from 4-(chloromethyl)benzoic acid. The inhibitory activities of the novel compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated. 3,4-Dihydroxy stilbene carbonyl compounds (7, 11b, 27b) inhibited PTP1B with IC50 values comparable to molybdate, while the conjugation-extended compound (15b) showed inhibition 3-fold better than preclinical RK682. The introduction of electron withdrawing groups or amides into the second phenyl ring, or extension of the conjugation into the stilbene molecule may increase stability of the generated radicals.
