8HLT

The co-crystal structure of DYRK2 with YK-2-99B

8HLT の概要

• エントリーDOI: 10.2210/pdb8hlt/pdb
• 分子名称: Dual specificity tyrosine-phosphorylation-regulated kinase 2, (6-{[(4P)-4-(1,3-benzothiazol-5-yl)-5-fluoropyrimidin-2-yl]amino}pyridin-3-yl)(piperazin-1-yl)methanone (2 entities in total)
• 機能のキーワード: inhibitor, cell cycle
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91387.48

構造登録者

Shen, H.T.,Xiao, Y.B.,Yuan, K.,Yang, P.,Li, Q.N. (登録日: 2022-12-01, 公開日: 2023-12-13, 最終更新日: 2024-10-23)

主引用文献

Yuan, K.,Shen, H.,Zheng, M.,Xia, F.,Li, Q.,Chen, W.,Ji, M.,Yang, H.,Zhuang, X.,Cai, Z.,Min, W.,Wang, X.,Xiao, Y.,Yang, P.
Discovery of Potent DYRK2 Inhibitors with High Selectivity, Great Solubility, and Excellent Safety Properties for the Treatment of Prostate Cancer.
J.Med.Chem., 66:4215-4230, 2023

PubMed Abstract: Prostate cancer (PCa) is a common male cancer with high incidence and mortality, and hormonal therapy as the major treatment for PCa patients is troubled by the inevitable resistance that makes us identify novel targets for PCa. Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) was found to be an effective target for the treatment of PCa, but the research on its inhibitors is rather little. In this work, a potent DYRK2 inhibitor (IC = 0.6 nM) was acquired through virtual screening and structural optimization, which displayed high selectivity among 205 kinases; meanwhile, detailed interactions of with DYRK2 were illustrated by the cocrystal. Furthermore, possessed great water solubility (29.5 mg/mL), favorable safety properties (LD > 10,000 mg/kg), and potent anti-PCa activities, which could be used as a potential candidate in further preclinical studies.

PubMed: 36800260
DOI: 10.1021/acs.jmedchem.3c00106

実験手法

X-RAY DIFFRACTION (2.8 Å)