Cyclin-Dependent Kinase Inhibitors as Marketed Anticancer Drugs: Where Are We Now? A Short Survey

Molecules

Gaëlle Mariaule¹ 

[1] Institut Curie, UMR CNRS 176, 26 rue d’Ulm, Paris 75005, France; E-Mail:

关键词: CDK;    kinase;    inhibitor;    anticancer;    heterocycle;    clinical evaluation;    ATP-competitive;    allosteric site;    ATP non-competitive;   

DOI  :  10.3390/molecules190914366

来源: mdpi

【 摘 要 】

In the early 2000s, the anticancer drug imatinib (Glivec^®) appeared on the market, exhibiting a new mode of action by selective kinase inhibition. Consequently, kinases became a validated therapeutic target, paving the way for further developments. Although these kinases have been thoroughly studied, none of the compounds commercialized since then target cyclin-dependent kinases (CDKs). Following a recent and detailed review on the subject by Galons et al., we concentrate our attention on an updated list of compounds under clinical evaluation (phase I/II/III) and discuss their mode of action as ATP-competitive inhibitors. CDK inhibition profiles and clinical development stages are reported for the 14 compounds under clinical evaluation. Also, tentative progress for forthcoming potential ATP non-competitive inhibitors and allosteric inhibitors are briefly described, along with their limitations.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.