Patricia J. Harvey

TL;DR: Results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors.

TL;DR: It is demonstrated that the modification of pyrido[2,3-d]pyrimidin-7-ones to include a 2-aminopyridine side chain at the C2-position provides inhibitors with exquisite selectivity for Cdk4/6 in vitro.

TL;DR: Oral administration of PF-00299804 causes significant antitumor activity, including marked tumor regressions in a variety of human tumor xenograft models that express and/or overexpress erbB family members or contain the double mutation (L858R/T790M) in ErbB1 (EGFR) associated with resistance to gefitinib and erlotinib.

TL;DR: It is reported that the introduction of a methyl substituent at the C-5 position of the pyrido[2,3-d]pyrimidin-7-one template is sufficient to confer excellent selectivity for Cdk4 vs other Cdks and representative tyrosine kinases.

TL;DR: Pharmacokinetic comparison of compounds 54 and 71 across three species selected compound 54 as the preferred candidate and has been assigned the nomenclature of dacomitinib and is currently under clinical evaluation.