Cancers 2015, 7, 179-237; doi:10.3390/cancers7010179 OPEN ACCESS cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review Targeting Cyclin-Dependent Kinases in Human Cancers: From Small Molecules to Peptide Inhibitors Marion Peyressatre †, Camille Prével †, Morgan Pellerano and May C. Morris * Institut des Biomolécules Max Mousseron, IBMM-CNRS-UMR5247, 15 Av. Charles Flahault, 34093 Montpellier, France; E-Mails:
[email protected] (M.P.);
[email protected] (C.P.);
[email protected] (M.P.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail:
[email protected]; Tel.: +33-04-1175-9624; Fax: +33-04-1175-9641. Academic Editor: Jonas Cicenas Received: 17 December 2014 / Accepted: 12 January 2015 / Published: 23 January 2015 Abstract: Cyclin-dependent kinases (CDK/Cyclins) form a family of heterodimeric kinases that play central roles in regulation of cell cycle progression, transcription and other major biological processes including neuronal differentiation and metabolism. Constitutive or deregulated hyperactivity of these kinases due to amplification, overexpression or mutation of cyclins or CDK, contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases therefore constitute biomarkers of proliferation and attractive pharmacological targets for development of anticancer therapeutics. The structural features of several of these kinases have been elucidated and their molecular mechanisms of regulation characterized in depth, providing clues for development of drugs and inhibitors to disrupt their function. However, like most other kinases, they constitute a challenging class of therapeutic targets due to their highly conserved structural features and ATP-binding pocket.