AN IN-SILICO APPROACH FOR DESIGNING POTENTIAL ANTAGONISTIC MOLECULES TARGETING CYCLIN-DEPENDENT KINASE HAVING THERAPEUTIC SIGNIFICANCE IN CANCER

Cancer is a preminent cause of death worldwide after heart disease. Although there are many types of cancer treatments, depending on the type of cancer and its stages, due to their complexity and adverse cytotoxic effects, some novel targets at the molecular level that are cancer-specific have become the area of research for more than a decade. Some targets have been identified, and CDKs are among them. They play a pivotal role in the cell cycle. This has directed to developing of novel Cyclin-Dependent Kinase Inhibitors with a major emphasis on designing compounds that can effectively inhibit the cell cycle progression in cancer by inhibiting the CDKs selectively, such as abemaciclib. In this study, we have generated and evaluated some CDKIs. These compounds were designed to target CDK6 (PDB ID: 5L2S). The bio-affinity values and binding modes of all designed analogs were evaluated and the pharmacokinetic profile (Caco-permeability, efflux, fdp, vdss, bbb parameters) was also examined. The study exhibited significant findings and analogs 10c, 20a and 34b with docking scores -12.11, -14.91, and -12.41 kcal/mol, respectively, were found to be more potent inhibitors of the CDK6 than abemaciclib (docking score -6.54) and also possess good pharmacokinetic profile. These findings proved them a good candidate for future research.