9OOJ

Crystal structure of MYST acetyltransferase domain in complex with inhibitor 18c

これはPDB形式変換不可エントリーです。

9OOJ の概要

• エントリーDOI: 10.2210/pdb9ooj/pdb
• 分子名称: Histone acetyltransferase KAT8, ZINC ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: acetyltransferase, inhibitor, complex, 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: 35121.10

構造登録者

Hermans, S.J.,Suwandi, A.,Parker, M.W.,Baell, J.B. (登録日: 2025-05-15, 公開日: 2026-02-11, 最終更新日: 2026-02-25)

主引用文献

Suwandi, A.,Jin, J.,Zhao, Y.,Mudududdla, R.,Gee, Y.S.,Deora, G.S.,Sun, Y.,Wei, H.,Huang, F.,He, J.S.,George, A.J.,Hermans, S.J.,Leaver, D.J.,Parker, M.W.,Baell, J.B.
Biological Activity and Structural Biology of Current KAT6A Inhibitor Chemotypes.
J.Med.Chem., 69:2082-2114, 2026

PubMed Abstract: All lysine acetyltransferases (KATs) modulate biological outcomes through the acetylation of lysine side-chain amino groups facilitated by acetyl coenzyme A (AcCoA). KAT6A belongs to the class of MYST domain histone acetyltransferases (HATs), which had been regarded as undruggable. The first on-target KAT6A inhibitors with activity were reported in 2018, catalyzing intense industry interest in this enzyme as an oncology target. In this study, we experimentally evaluated representative KAT6A inhibitor chemotypes through resynthesis and comparative biochemical assays, cellular assays, and structural biology. We outline the recent history of each KAT6A inhibitor chemotype discovery, including SAR for potency, selectivity, and cellular activity. We extensively benchmark key compounds from each chemotype, augmented by new acylsulfonohydrazide analogues and a novel fused [1,2,4]thiadiazine KAT6A inhibitor subclass, which we report here for the first time, along with co-crystal structures. Additionally, we report on the activity, pharmacokinetics, and toxicology profiles of these inhibitors.

PubMed: 41611522
DOI: 10.1021/acs.jmedchem.5c01426

実験手法

X-RAY DIFFRACTION (1.82 Å)