2. Academic Validation
  3. Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors

Pyrido[2,3-d]pyrimidines: discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors

  • Bioorg Med Chem Lett. 2013 Dec 15;23(24):6610-5. doi: 10.1016/j.bmcl.2013.10.055.
Kevin Anderson 1,  Yi Chen,  Zhi Chen,  Romyr Dominique,  Kelli Glenn,  Yang He,  Cheryl Janson,  Kin-Chun Luk,  Christine Lukacs,  Ann Polonskaia,  Qi Qiao,  Aruna Railkar,  Pamela Rossman,  Hongmao Sun,  Qing Xiang,  Masha Vilenchik,  Peter Wovkulich,  Xiaolei Zhang
Affiliations

Affiliation

  • 1 Discovery Chemistry, Hoffmann-La Roche Inc., pRED, Pharma Research & Early Development, 340 Kingsland Street, Nutley, NJ 07110, USA.
PMID: 24239188 DOI: 10.1016/j.bmcl.2013.10.055
Abstract

DYRK1B is a kinase over-expressed in certain Cancer cells (including colon, ovarian, pancreatic, etc.). Recent publications have demonstrated inhibition of DYRK1B could be an attractive target for Cancer therapy. From a data-mining effort, the team has discovered analogues of pyrido[2,3-d]pyrimidines as potent enantio-selective inhibitors of DYRK1B. Cells treated with a tool compound from this series showed the same cellular effects as down regulation of DYRK1B with siRNA. Such effects are consistent with the proposed mechanism of action. Progress of the SAR study is presented.

Keywords

Anti-cancer; DYRK1A; DYRK1B; Kinase-inhibitor; Pyrido[2,3-d]pyrimidine.

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