5ZAN

Crystal Structure of Aurora-A in complex with a new Quinazoline inhibitor

5ZAN の概要

• エントリーDOI: 10.2210/pdb5zan/pdb
• 分子名称: Aurora kinase A, 7-(4-methylpiperazin-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(E)-2-phenylethenyl]quinazolin-4-amine (2 entities in total)
• 機能のキーワード: drug design, transferase, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32985.88

構造登録者

Cheng, B.,Lu, G.,Zhou, H. (登録日: 2018-02-07, 公開日: 2019-02-13, 最終更新日: 2025-09-24)

主引用文献

Long, L.,Zhang, B.,Peng, W.,Pan, Y.,Zhai, H.,Cheng, B.,Tu, Z.,Long, Z.,Zhou, H.,Liu, Q.,Lu, G.
Optimization of Novel Quinazolines as Potent Aurora Kinase Inhibitors for Triple-Negative Breast Cancer Treatment.
J.Med.Chem., 68:18197-18215, 2025

PubMed Abstract: This work describes the discovery of a new series of Aurora kinase inhibitors based on quinazoline skeleton derived from , as well as the first X-ray cocrystal structure complexes of vinyl-quinazoline with Aurora A. Replacing pyrimidine with quinazoline improved anticancer activity and facilitated cocrystal formation. Compounds and showed excellent Aurora A kinase inhibition, with IC values of 6.0 and 2.8 nM, respectively. demonstrated superior activity against TNBC MDA-MB-231 cells with an IC value of 48 nM and achieved 59% tumor growth inhibition in xenograft models, vs 's 33% with no observable toxicity. Mechanistic studies using immunoblotting, immunofluorescence staining, and flow cytometry showed that outperforms in inhibiting Aurora A kinase activation, preventing spindle formation, arresting the cell cycle, and inducing cell apoptosis. Thus, has the potential for further optimization and is a promising anticancer drug candidate.

PubMed: 40852972
DOI: 10.1021/acs.jmedchem.5c00107

実験手法

X-RAY DIFFRACTION (2.85 Å)