Anticancer Drug Design: Development of Cyclin-Dependent KinaseInhibitors Using In Silico Techniques

Abstract

In mammalian cells, proliferation is controlled by the cell cycle, where cyclin-dependent kinases regulate critical checkpoints. CDK4 is considered highly validated anticancer drug target due to its essential role regulating cell cycle progression at the G1 restriction point. Our objective is designing novel CDK4 inhibitors using Structure-Based Drug Design and Quantitative Structure-Activity Relationship techniques. We used bioinformatics tools and biological databases. QSAR study of CDK4 inhibitors has given us an idea on the physicochemical features of studied compounds and their correlation with the IC50 activity. The docking study has helped to highlight the molecule key elements to refine in order to get a more potent compound of CDK4.The Molecule under the code 21366124 which has the low IC50= 3 nmole shows the most binding affinity with score value of ΔG=-9,8 kcal/mol. As prospects, it would be very interesting to synthesize this drug candidate and to test its inhibitory activity on cell culture of breast cancer.