title: Cyclin-dependent kinase inhibitors as marketed anticancer drugs: where are we now? A short survey.
abstract: 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.
authors.affiliation: Institut Curie, UMR CNRS 176, 26 rue d'Ulm, Paris 75005, France. gaelle.mariaule@curie.fr.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Mariaule
authors.affiliation: Institut Curie, UMR CNRS 176, 26 rue d'Ulm, Paris 75005, France. philippe.belmont@parisdescartes.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Belmont
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001549:Benzamides / Q000737:chemistry / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D000068877:Imatinib Mesylate; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000737:chemistry / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D018844:Cyclin-Dependent Kinases