2. Academic Validation
  3. Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315

Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315

  • Bioorg Med Chem Lett. 2013 Jun 15;23(12):3654-61. doi: 10.1016/j.bmcl.2013.02.096.
Thomas C Coombs 1,  Cordelle Tanega,  Min Shen,  Jenna L Wang,  Douglas S Auld,  Samuel W Gerritz,  Frank J Schoenen,  Craig J Thomas,  Jeffrey Aubé
Affiliations

Affiliation

  • 1 University of Kansas Specialized Chemistry Center, University of Kansas, Lawrence, KS 66047, USA.
PMID: 23642479 DOI: 10.1016/j.bmcl.2013.02.096
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.

Figures
Products