| Literature DB >> 21982796 |
Stuart C Wilson1, Butrus Atrash, Clare Barlow, Susan Eccles, Peter M Fischer, Angela Hayes, Lloyd Kelland, Wayne Jackson, Michael Jarman, Amin Mirza, Javier Moreno, Bernard P Nutley, Florence I Raynaud, Peter Sheldrake, Mike Walton, Robert Westwood, Steven Whittaker, Paul Workman, Edward McDonald.
Abstract
The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound αSβR-21 inhibits CDK2/cyclin E with IC(50)=30 nM, CDK7-cyclin H with IC(50)=1.3 μM, and CDK9-cyclinT with IC(50)=0.11 μM; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI(50)=0.7 μM; and shows antitumour activity when dosed p.o. at 50mg/kg to mice bearing HCT116 solid human tumour xenografts.Entities:
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Year: 2011 PMID： 21982796 DOI： 10.1016/j.bmc.2011.08.051
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641