Selective ATP competitive leads of CDK4: Discovery by 3D-QSAR pharmacophore mapping and molecular docking approach |
| |
| Institution: | 1. Molecular Modeling Research Laboratory, Department of Chemistry, University College of Science, Osmania University, Hyderabad 500007, Telangana, India;2. Department of Chemistry, South Valley University, Qena 83523, Egypt;3. Department of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad, Telangana, India;1. Institute of Chemical Sciences, University of Peshawar, Peshawar-25120, Pakistan;2. State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, China;3. State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China;4. Beijing Key Lab of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, 15 Bei San Huan East Road, P.O. Box 53, Beijing 100029, China;1. School of Mathematics and Information Science, Xianyang Normal University, Wenlin Road, Xianyang, 712000, China;2. Department of Computer and Information Science, Fordham University, Lincoln Center, New York, NY, 10023, USA;1. Key Laboratory of Advanced Design and Intelligent Computing, Ministry of Education, Dalian University, Dalian, 116622, China;2. School of Computer Science and Technology, Dalian University of Technology, Dalian, 116024, China;1. Centre for Molecular Cancer Research (CMCR), Vishnu Institute of Pharmaceutical Education and Research, Narsapur, India;2. Clinical Research Department, Emcure Pharmaceuticals Ltd., Pune, India;3. Department of Pharmaceutical Chemistry, Sultan Ul Uloom College of Pharmacy, Hyderabad, India;4. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands;5. Department of Pharmaceutical Chemistry, Gland Institute of Pharmaceutical Sciences, Narsapur, India |
| |
| Abstract: | The discovery of ATP competitive CDK4 inhibitors is an on-going challenging task in cancer therapy. Here, an attempt has been made to develop new leads targeting ATP binding site of CDK4 by applying 3D-QSAR pharmacophore mapping and molecular docking methods The outcome of 6 leads offers a significant contribution for selective CDK4 inhibition, since they show potential binding interactions with Val96, Arg101, and Glu144 residues of CDK4, that are unique and from other kinases. It is worth noting that there is a striking similarity in binding interactions of the leads and known CDK4 inhibitors, namely Abemaciclib, Palbociclib and Ribociclib. Further key features, including high dock score value, good predicted activity, scaffold diversity, and the acceptable ADME profile of leads, provide a great opportunity for the development of highly potent and selective ATP competitive inhibitors of CDK4. |
| |
| Keywords: | CDK4 ATP competitive inhibitors 3D-QSAR pharmacophore Virtual screening Docking ADME |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
