School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System & Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology & Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, PR China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, PR China.
Future Med Chem. 2021 May;13(9):839-858. doi: 10.4155/fmc-2020-0376. Epub 2021 Apr 6.
Microtubules have been a concerning target of cancer chemotherapeutics for decades, and several tubulin-targeted agents, such as paclitaxel, vincristine and vinorelbine, have been approved. The colchicine binding site is one of the primary targets on microtubules and possesses advantages compared with other tubulin-targeted agents, such as inhibitors of tumor vessels and overcoming P-glycoprotein overexpression-mediated multidrug resistance. This study reviews and summarizes colchicine binding site inhibitors reported in recent years with structural studies via the crystal structures of complexes or computer simulations to discover new lead compounds. We are attempting to resolve the challenge of colchicine site agent research.
微管数十年来一直是癌症化疗药物的关注靶点，已有数种微管蛋白靶向药物（如紫杉醇、长春新碱和长春瑞滨）获得批准。秋水仙碱结合位点是微管的主要靶点之一，与其他微管蛋白靶向药物（如肿瘤血管抑制剂和克服 P-糖蛋白过表达介导的多药耐药性）相比具有优势。本研究通过复合物的晶体结构或计算机模拟的结构研究，综述和总结了近年来报道的秋水仙碱结合位点抑制剂，以发现新的先导化合物。我们正试图解决秋水仙碱位点药物研究的难题。
