R547

Cyclin-dependent kinases (Cdks) are critical positive regulators of cell cycle progression and cellular transcription whose dysregulation can lead to the development of cancer. R547 is a diaminopyrimidine compound that inhibits Cdk1/cyclin B, Cdk2/cyclin E, and Cdk4/cyclin D1 (Kis = 1-3 nM).{29463} It is inactive against a panel of more than 120 unrelated kinases (Kis > 5 µM).{29463} R547 inhibits tumor cell proliferation (IC50s ? 0.6 µM in vitro), inducing cell cycle arrest at G1 and G2 phases and apoptosis as well as reducing phosphorylation of the retinoblastoma protein.{29463} It also demonstrates antitumor activity in vivo in various human tumor xenograft models.{29463}