Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe …

…, SW Gerritz, FJ Schoenen, CJ Thomas, J Aubé

Index: Coombs, Thomas C.; Tanega, Cordelle; Shen, Min; Wang, Jenna L.; Auld, Douglas S.; Gerritz, Samuel W.; Schoenen, Frank J.; Thomas, Craig J.; Aube, Jeffrey Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 12 p. 3654 - 3661

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Citation Number: 19

Abstract

Substituted pyrimidine inhibitors of the Clk and Dyrk kinases have been developed, exploring structure–activity relationships around four different chemotypes. The most potent compounds have low-nanomolar inhibitory activity against Clk1, Clk2, Clk4, Dyrk1A and Dyrk1B. Kinome scans with 442 kinases using agents representing three of the chemotypes show these inhibitors to be highly selective for the Clk and Dyrk families. Further off-target ...