Expression patterns and therapeutic implications of CDK4 across multiple carcinomas: a molecular docking and MD simulation study

Abstract

The CDKs are known to play a critical role in cell cycle regulation process. Among the different groups of CDKs, CDK4 overexpression/hyperactivation is found to be present in many cancers and a specific CDK4 inhibitor, palbociclib has been recently approved by the FDA against breast cancer. However, the treatment with palbociclib has shown many associated toxicities such as-anemia, thrombocytopenia, neutropenia, and febrile neutropenia and more. Despite the fact being FDA approved for only breast cancer and no other cancers and CDK4 being overexpressed in multiple cancers. Therefore, we in our study intend to screen two novel CDK4 inhibitors that show considerably less associated toxicities and greater therapeutic implications than palbociclib. We screened the compounds using Lipinski's rule, ADMET analysis and further analyzed the selected compounds using a virtual screening method called molecular docking and validated our results by MD simulation. We studied the expression patterns and prognostic significance of CDK4 across multiple carcinomas by using some database like UALCAN, cBioportal, and KM-Plotter.

Keywords: ADMET; CDK4; MD simulation; Molecular docking; Palbociclib; Pan-cancer.