2​ Biological Activity R547 is a novel, selective inhibitor of cell cycle and transcriptional cyclin dependent kinases with a Ki of median 2 nM for CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1. In vivo, R547 showed antitumor activity. The selective kinase inhibition profile and the preclinical antitumor activity of R547 suggest that it may be promising for development for use in the treatment of solid tumors. The cyclin-dependent protein kinases are key regulators of cell cycle progression. Aberrant expression or altered activity of distinct cyclin-dependent kinase (CDK) complexes leads to escape of cells from cell cycle control, leading to unrestricted cell proliferation. CDK inhibitors have the potential to induce cell cycle arrest and apoptosis in cancer cells, and identifying small-molecule CDK inhibitors has been a major focus in cancer research. In cell-free assays, R547 was inactive (K(i) > 5,000 nM) against a panel of >120 unrelated kinases. In vitro, R547 effectively prevented the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC50 < 0.60 μM. [1] 3​ References: In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. DePinto W et al. Mol Cancer Ther. 2006 Nov;5(11):2644-58. The pharmacological and toxicological properties of this product have not been fully investigated. Exercise caution in use and handling. This product must not be used in humans.