2. Academic Validation
  3. Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

  • Bioorg Med Chem. 2011 Nov 15;19(22):6949-65. doi: 10.1016/j.bmc.2011.08.051.
Stuart C Wilson 1,  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
Affiliations

Affiliation

  • 1 Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, UK.
PMID: 21982796 DOI: 10.1016/j.bmc.2011.08.051
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-123826
    CDK Inhibitor
    CDK