[4-Amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl](2,3-difluoro-6-methoxyphenyl)methanone(R 547)

Описание

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 (K_is = 1-3 nM). It is inactive against a panel of more than 120 unrelated kinases (K_is > 5 μM). 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. It also demonstrates antitumor activity in vivo in various human tumor xenograft models.