PD0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (~0.011 µM) and Cdk6 (~0.016 µM), having no activity against a panel of 36 additional protein kinases. PD0332991 causes elimination of phospho-Rb and the proliferative marker Ki-67 in tumor tissue and downregulation of genes under the transcriptional control of E2F. It has showed significant inhibition in a broad spectrum of human tumor xenografts in vivo.