9N3N

Crystal structure of PRMT5:MEP50 in complex with MTA and oxamide compound 3

これはPDB形式変換不可エントリーです。

9N3N の概要

• エントリーDOI: 10.2210/pdb9n3n/pdb
• 分子名称: Protein arginine N-methyltransferase 5, Methylosome protein 50, 5'-DEOXY-5'-METHYLTHIOADENOSINE, ... (9 entities in total)
• 機能のキーワード: inhibitor, mta-cooperative, mtap null, transferase, transferase-inhibitor complex, transferase/inhibitor
• 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: 113838.20

構造登録者

Whittington, D.A. (登録日: 2025-01-31, 公開日: 2025-03-12, 最終更新日: 2025-03-19)

主引用文献

Cottrell, K.M.,Briggs, K.J.,Tsai, A.,Tonini, M.R.,Whittington, D.A.,Gong, S.,Liang, C.,McCarren, P.,Zhang, M.,Zhang, W.,Huang, A.,Maxwell, J.P.
Discovery of TNG462: A Highly Potent and Selective MTA-Cooperative PRMT5 Inhibitor to Target Cancers with MTAP Deletion.
J.Med.Chem., 68:5097-5119, 2025

PubMed Abstract: The gene encoding for MTAP is one of the most commonly deleted genes in cancer, occurring in approximately 10-15% of all human cancer. We have previously described the discovery of TNG908, a brain-penetrant clinical-stage compound that selectively targets -deleted cancer cells by binding to and inhibiting PRMT5 cooperatively with MTA, which is present in elevated concentrations in -deleted cells. Herein we describe the discovery of TNG462, a more potent and selective MTA-cooperative PRMT5 inhibitor with improved DMPK properties that is selective for -deleted cancers and is currently in Phase I/II clinical trials.

PubMed: 40035511
DOI: 10.1021/acs.jmedchem.4c03067

実験手法

X-RAY DIFFRACTION (2.75 Å)