Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591746 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
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 pharmacological evaluation with ML315, the most selective agent, supports this conclusion.
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Authors
Thomas C. Coombs, Cordelle Tanega, Min Shen, Jenna L. Wang, Douglas S. Auld, Samuel W. Gerritz, Frank J. Schoenen, Craig J. Thomas, Jeffrey Aubé,