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In Vitro and in Vivo Activity of R547: A Potent and Selective Cyclin-Dependent Kinase Inhibitor Currently in Phase I Clinical Trials

In Vitro and in Vivo Activity of R547: A Potent and Selective Cyclin-Dependent Kinase Inhibitor Currently in Phase I Clinical Trials

Wanda DePinto, Xin-Jie Chu, Xuefeng Yin, Melissa Smith, Kathryn Packman, Petra Goelzer, Allen Lovey, Yingsi Chen, Hong Qian, Rachid Hamid, Qing Xiang, Christian Tovar, Roger Blain, Tom Nevins, Brian Higgins, etc.

Mol Cancer Ther. 2006 Nov;5(11):2644-58.

PMID: 17121911

Abstract:

The cyclin-dependent protein kinases are key regulators of cell cycle progression. Aberrant expression or altered activity of distinct cyclin-dependent kinase (CDK) complexes results in 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. Several CDK inhibitors are entering the clinic, the most recent being selective CDK2 and CDK4 inhibitors. We have identified a diaminopyrimidine compound, R547, which is a potent and selective ATP-competitive CDK inhibitor. In cell-free assays, R547 effectively inhibited CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1 (K(i) = 1-3 nmol/L) and was inactive (K(i) > 5,000 nmol/L) against a panel of >120 unrelated kinases. In vitro, R547 effectively inhibited the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC(50)s

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP741713406	R547		741713-40-6	Price

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