4MQ1

The crystal structure of DYRK1a with a bound pyrido[2,3-d]pyrimidine inhibitor

4MQ1 の概要

• エントリーDOI: 10.2210/pdb4mq1/pdb
• 関連するPDBエントリー: 2vx3 4MQ2
• 分子名称: Dual specificity tyrosine-phosphorylation-regulated kinase 1A, N-(5-{[(1R)-3-amino-1-(3-chlorophenyl)propyl]carbamoyl}-2-chlorophenyl)-2-methoxy-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• 機能のキーワード: dyrk1a, dyrk1b, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus speckle: Q13627
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 172689.86

構造登録者

Lukacs, C.M.,Janson, C.A.,Garvie, C.,Liang, L. (登録日: 2013-09-15, 公開日: 2013-12-11, 最終更新日: 2023-12-06)

主引用文献

Anderson, K.,Chen, Y.,Chen, Z.,Dominique, R.,Glenn, K.,He, Y.,Janson, C.,Luk, K.C.,Lukacs, C.,Polonskaia, A.,Qiao, Q.,Railkar, A.,Rossman, P.,Sun, H.,Xiang, Q.,Vilenchik, M.,Wovkulich, P.,Zhang, X.
Pyrido[2,3-d]pyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors.
Bioorg.Med.Chem.Lett., 23:6610-6615, 2013

PubMed 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.

PubMed: 24239188
DOI: 10.1016/j.bmcl.2013.10.055

実験手法

X-RAY DIFFRACTION (2.35 Å)