8H6T

Complex structure of CDK2/Cyclin E1 and a potent, selective small molecule inhibitor

8H6T の概要

• エントリーDOI: 10.2210/pdb8h6t/pdb
• 関連するPDBエントリー: 8H6O 8H6P
• 分子名称: Cyclin-dependent kinase 2, G1/S-specific cyclin-E1, (1R,3S)-3-{3-[(pyridin-2-yl)amino]-1H-pyrazol-5-yl}cyclopentyl propan-2-ylcarbamate, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, selective, anti-tumor, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66082.70

構造登録者

Ren, X. (登録日: 2022-10-18, 公開日: 2023-02-22, 最終更新日: 2024-11-20)

主引用文献

Yu, Y.,Huang, J.,He, H.,Han, J.,Ye, G.,Xu, T.,Sun, X.,Chen, X.,Ren, X.,Li, C.,Li, H.,Huang, W.,Liu, Y.,Wang, X.,Gao, Y.,Cheng, N.,Guo, N.,Chen, X.,Feng, J.,Hua, Y.,Liu, C.,Zhu, G.,Xie, Z.,Yao, L.,Zhong, W.,Chen, X.,Liu, W.,Li, H.
Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design.
Acs Med.Chem.Lett., 14:297-304, 2023

PubMed Abstract: Selective CDK2 inhibitors have the potential to provide effective therapeutics for CDK2-dependent cancers and for combating drug resistance due to high cyclin E1 (CCNE1) expression intrinsically or CCNE1 amplification induced by treatment of CDK4/6 inhibitors. Generative models that take advantage of deep learning are being increasingly integrated into early drug discovery for hit identification and lead optimization. Here we report the discovery of a highly potent and selective macrocyclic CDK2 inhibitor QR-6401 () accelerated by the application of generative models and structure-based drug design (SBDD). QR-6401 () demonstrated robust antitumor efficacy in an OVCAR3 ovarian cancer xenograft model via oral administration.

PubMed: 36923916
DOI: 10.1021/acsmedchemlett.2c00515

実験手法

X-RAY DIFFRACTION (3 Å)