机构：[1]Department of Respiratory & Critical Care Medicine, Targeted Tracer Research & development laboratory, West China Hospital, Sichuan University, Chengdu, 610041, China四川大学华西医院[2]Cancer Center, West China Hospital, Sichuan University & Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China四川大学华西医院[3]Laboratory of Clinical Proteomics & Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 88 Keyuan South Road, Hi-Tech Zone, Chengdu, 610041, China四川大学华西医院[4]Department of Nuclear Medicine, Nuclear Medicine & Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China[5]Biomedical research center, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, P.R. China.North Sichuan Medical College, Nanchong, China
Background: Tubulin protein is a promising target for antitumor drugs. Some tubulin inhibitors targeting the colchicine binding site are not substrates of the multidrug-resistance efflux pump, which can overcome the mechanism of drug resistance mediated by P-glycoprotein. Methodology/results: SSE15206 is a colchicine binding site inhibitor with antiproliferative activity against different drug-resistant cell lines. Unfortunately, the lack of detailed interaction information about SSE15206 in complex with tubulin impeded the development of potent drugs that possess similar scaffolds. Herein, the authors report the crystal structure of the tubulin-SSE15206 complex at a resolution of 2.8 Å. Conclusion: The complex structure reveals the intermolecular interactions between SSE15206 and tubulin, providing a rationale for the development of pyrazolinethioamides as tubulin polymerization inhibitors and to overcome multidrug resistance.
基金：
This work was supported by the National Natural Science Foundation of China (31900866 to J Feng), the Doctors’ Start-up and
Initiation Grants of the Affiliated Hospital of Southwest Medical University (16227 to J Feng) and the research funding of the
Southwest Medical University (00031020 to J Feng).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|4 区药物化学
最新[2023]版：
大类|4 区医学
小类|4 区药物化学
第一作者：
第一作者机构：[1]Department of Respiratory & Critical Care Medicine, Targeted Tracer Research & development laboratory, West China Hospital, Sichuan University, Chengdu, 610041, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Respiratory & Critical Care Medicine, Targeted Tracer Research & development laboratory, West China Hospital, Sichuan University, Chengdu, 610041, China[2]Cancer Center, West China Hospital, Sichuan University & Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
推荐引用方式(GB/T 7714)：
Ma Lingling,Lei Jiahong,Chen Hai,et al.Structural insight into SSE15206 in complex with tubulin provides a rational design for pyrazolinethioamides as tubulin polymerization inhibitors.[J].Future medicinal chemistry.2022,doi:10.4155/fmc-2021-0124.
APA：
Ma Lingling,Lei Jiahong,Chen Hai,Huang Ridong,Su Tao...&Sun Qiu.(2022).Structural insight into SSE15206 in complex with tubulin provides a rational design for pyrazolinethioamides as tubulin polymerization inhibitors..Future medicinal chemistry,,
MLA：
Ma Lingling,et al."Structural insight into SSE15206 in complex with tubulin provides a rational design for pyrazolinethioamides as tubulin polymerization inhibitors.".Future medicinal chemistry .(2022)
