9Q8A

Crystal structure of the human METTL3-METTL14 in complex with small molecule inhibitor Compound 3

これはPDB形式変換不可エントリーです。

9Q8A の概要

• エントリーDOI: 10.2210/pdb9q8a/pdb
• 関連するPDBエントリー: 9IH5 9Q89
• 分子名称: N(6)-adenosine-methyltransferase catalytic subunit METTL3, N(6)-adenosine-methyltransferase non-catalytic subunit METTL14, (3~{R})-~{N}-(cyclopropylmethyl)-1-[6-[3-[4-(5-cyclopropylpyridin-3-yl)-1,2,3-triazol-1-yl]oxetan-3-yl]pyridin-3-yl]piperidin-3-amine, ... (4 entities in total)
• 機能のキーワード: mettl3 mettl14 inhibitor, epics, rna binding protein
• 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: 57224.45

構造登録者

Dutheuil, G.,Oukoloff, K. (登録日: 2025-02-24, 公開日: 2026-04-22, 最終更新日: 2026-05-06)

主引用文献

Dutheuil, G.,Oukoloff, K.,Lenoir, F.,Korac, J.,El Bousmaqui, M.,Probst, N.,Lapin, A.,Nakhabina, G.,Parmentier, N.,Sorlet, C.,Fraser, G.L.
Optimization of METTL3 Inhibitors for the Treatment of Solid Tumors and AML.
J.Med.Chem., 69:9585-9602, 2026

PubMed Abstract: Further lead optimization of our series of METTL3 inhibitors is disclosed where aggregative replacements of the α-methylpyridone core and 5-dimethylaminopyridin-3-yl-1,2,3-triazole hinge moiety with an oxetan-3-yl-pyridin-3-yl core and 5-cyclopropylpyridin-3-yl-1,3,4-thiadiazol-2-yl hinge moiety, respectively, improved oral bioavailability while decreasing lipophilicity, thereby translating into oral efficacy in mouse tumor models. This research culminates in the discovery of , a compound with a clear selectivity profile and a favorable ADME/PK profile in addition to robust efficacy in AML and solid tumor models. has entered clinical development for the treatment of advanced solid tumors.

PubMed: 41978353
DOI: 10.1021/acs.jmedchem.6c00474

実験手法

X-RAY DIFFRACTION (1.95 Å)