典型文献
Discovery of 4-Thiazol-N-(pyridin-2-yl)pyrimidin-2-amine as Novel Cyclin-dependent Kinases 4 and 6 Dual Inhibitors via 3D-QSAR and Molecular Simulation
文献摘要：
Cyclin D dependent kinases 4/6 regulate the entry of cells into S phase and are effective target for the discovery of anticancer drugs.In this article,3D-QSAR modeling including comparative molecular field analy-sis(CoMFA)and comparative molecular similarity indices analysis fields(CoMSIA)was implemented on 52 dual CDK4/6 inhibitors.As a result,we obtained a pretty good 3D-QSAR model,which is CoMFACDK4 with q2 to be 0.543 and r2 to be 0.967;CoMSIACDK4 with q2 being 0.518 and r2 being 0.937;CoMFAcDK6 with q2 to be 0.624 and r2 to be 0.984;CoMSIACDK6 with q2 being 0.584 and r2 being 0.975.Molecular docking confirmed the important residues for interactions.Molecular dynamics simulation further confirmed binding affinity with key residues of protein,such as Lys22,Lys35,Val96 for CDK4 and Lys43,His100,Val101 for CDK6 at the active sites.Then these results offered new directions to explore new inhibitors of CDK4/6.Finally,we designed 10 novel compounds with promising expected activity and ADME/T properties,and provided referable synthetic routes.
文献关键词：
中图分类号：
作者姓名：
FU Le;ZHAO Li-Nan;GUO Hong-Mei;YU Na;QUAN Wen-Xuan;CHEN Yi;SHU Mao;WANG Rui;LIN Zhi-Hua
作者机构：
School of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China;Qianjiang Central Hospital of Chongqing,Chongqing 409099,China
文献出处：
引用格式：
[1]FU Le;ZHAO Li-Nan;GUO Hong-Mei;YU Na;QUAN Wen-Xuan;CHEN Yi;SHU Mao;WANG Rui;LIN Zhi-Hua-.Discovery of 4-Thiazol-N-(pyridin-2-yl)pyrimidin-2-amine as Novel Cyclin-dependent Kinases 4 and 6 Dual Inhibitors via 3D-QSAR and Molecular Simulation)[J].结构化学,2022(03):108-124
A类：
Thiazol,CoMFACDK4,CoMSIACDK4,CoMFAcDK6,CoMSIACDK6,Lys22,Lys35,Val96,Lys43,His100,Val101,referable
B类：
Discovery,pyridin,yl,pyrimidin,amine,Novel,Cyclin,dependent,Kinases,Dual,Inhibitors,via,QSAR,Molecular,Simulation,kinases,regulate,entry,cells,into,phase,are,effective,target,discovery,anticancer,drugs,this,article,modeling,including,comparative,molecular,similarity,indices,analysis,fields,was,implemented,dual,inhibitors,we,obtained,pretty,good,which,q2,r2,being,docking,confirmed,important,residues,interactions,dynamics,simulation,further,binding,affinity,key,protein,such,active,sites,Then,these,results,offered,new,directions,explore,Finally,designed,novel,compounds,promising,expected,activity,ADME,properties,provided,synthetic,routes
AB值：
0.491667
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机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
