Discovery Chemistry, Hoffmann-La Roche Inc., pRED, Pharma Research & Early Development, 340 Kingsland Street, Nutley, NJ 07110, USA.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6610-5. doi: 10.1016/j.bmcl.2013.10.055. Epub 2013 Nov 1.
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.
DYRK1B 是一种在某些癌细胞（包括结肠、卵巢、胰腺等）中过度表达的激酶。最近的出版物表明，抑制 DYRK1B 可能是癌症治疗的一个有吸引力的靶点。通过数据挖掘，该团队发现了吡啶并[2,3-d]嘧啶类似物作为 DYRK1B 的有效对映选择性抑制剂。用该系列的工具化合物处理的细胞表现出与 DYRK1B 下调 siRNA 相同的细胞效应。这些效应与所提出的作用机制一致。本文介绍了 SAR 研究的进展。
