PCC0208017,a novel small-molecule inhibitor of MARK3/MARK4,suppresses glioma progression in vitro and in vivo
PCC0208017, MARK3/MARK4 的一个新奇小分子的禁止者,压制 glioma 前进在 ? vitro 并且在里面 ? vivo作者机构:School of PharmacyKey Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs inUniversities of ShandongYantai UniversityYantai 264005China Department of Clinical MedicineBinzhou Medical CollegeYantai 256603China GRU Cancer CenterAugusta UniversityAugustaGA 30912USA
出 版 物:《Acta Pharmaceutica Sinica B》 (药学学报(英文版))
年 卷 期:2020年第10卷第2期
页 面:289-300页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 10[医学]
基 金:partially supported by National Science Foundation of China(NSFC,81728020) Key Research Project of Shandong Province(2017GSF18177,China) Natural Science Foundation of Shandong Province(ZR2018LH025,China) The Science and Technology Support Program for Youth Innovation in Universities of Shandong(2019KJM009) Key Research Project of Yantai(2019XDHZ102,China) Taishan Scholar Project
主 题:Glioma PCC0208017 MARK3 MARK4 Molecular docking
摘 要:Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for ***,we report a novel dual small-molecule inhibitor of MARK3 and MARK4,designated as *** vitro,PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4,and strongly reduced proliferation in three glioma cell *** compound attenuated glioma cell migration,glioma cell invasion,and *** mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau,disrupted microtubule dynamics,and induced a G2/M phase cell cycle *** an in vivo glioma model,PCC0208017 showed robust anti-tumor activity,blood-brain barrier permeability,and a good oral pharmacokinetic *** docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and *** together,our study describes for the first time that PCC0208017,a novel MARK3/MARK4 inhibitor,might be a promising lead compound for treatment of glioma.