Combined Ligand and Structure Based Approaches for Narrowing on the Essential Physicochemical Characteristics for CDK4 Inhibition

The cell cycle events are well coordinated resulting in proper DNA replication, leading to healthy daughter cells. The cell cycle is a frequent target of genetic alterations in cancer because of its central role in the control of cell growth and proliferation. The central players in the cell cycle machinery are Cyclin-Dependent Kinases (CDKs). CDKs are a family of heterodimeric serine/threonine kinases consisting of a catalytic CDK and an activating cyclin subunit. In mammals, there are different CDKs controlling different stages of the cell cycle and play the role of switch on/off on the cell cycle process. When on, the cell passes through the stage that the particular CDK controls, while when off, the cell cycle stops when it reaches the stage controlled by that CD