High-throughput virtual screening followed by in vitro investigation to identify new lead inhibitors of Cyclin Dependent Kinase 4

In the family of serine/threonine kinases, Cyclin Dependent Kinase 4 (CDK4), is an important regulator in numerous signal transduction pathways. The cell cycle is dysregulated in human breast adenocarcinoma (MCF7). A set of various categorical QSAR models were generated and validated in the current examination. A recursive partition model, with predictive ability shown by an accuracy of greater than 0.90, was used for virtual screening of 500,000 molecules. Following a consecutive series of molecular docking procedures, followed by pharmacokinetic analysis of 49759 molecules predicted to have pIC50 greater than 7.39, 25 molecules displayed properties that could be described as drug-like. We selected the lead molecules in the MCF-7 cell line based on its ability to promote cell cycle progression.