Third-generation CDK inhibitors: A review on the synthesis and binding modes of Palbociclib, Ribociclib and Abemaciclib

The role of cyclin-dependent kinases (CDKs) in regulating the transition of cell cycle steps makes thisclass of enzymes a suitable target for cancer therapy. Three different generations of CDKs inhibitors havebeen developed so far. Third-generation compounds (i.e.selective CDK4/6 inhibitors) are the mostpromising ones, due to their limited toxicity and highin vivoactivity. To date, three compounds haveentered the therapy, namely Palbociclib, Ribociclib and Abemaciclib. Herein we review the medicinalchemistry aspects of these drugs, with some references to very similar analogues that have been published