title: Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 1: identification and optimisation of substituted 4,6-bis anilino pyrimidines.
abstract: Using a high-throughput screening campaign, we identified the 4,6-bis anilino pyrimidines as inhibitors of the cyclin-dependent kinase, CDK4. Herein we describe the further chemical modification and use of X-ray crystallography to develop potent and selective in vitro inhibitors of CDK4.
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Beattie
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Breault
authors.forename: Rebecca P A
authors.initials: RP
authors.lastname: Ellston
authors.forename: Stephen
authors.initials: S
authors.lastname: Green
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Jewsbury
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Midgley
authors.forename: Russell T
authors.initials: RT
authors.lastname: Naven
authors.forename: Claire A
authors.initials: CA
authors.lastname: Minshull
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pauptit
authors.forename: Julie A
authors.initials: JA
authors.lastname: Tucker
authors.forename: J Elizabeth
authors.initials: JE
authors.lastname: Pease
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases