9FKR

KAT6A IN COMPLEX WITH SMALL MOLECULE INHIBITOR BAY-184

これはPDB形式変換不可エントリーです。

9FKR の概要

• エントリーDOI: 10.2210/pdb9fkr/pdb
• 分子名称: Histone acetyltransferase KAT6A, ZINC ION, 6-(dimethylamino)-~{N}-(2-phenylphenyl)sulfonyl-1-benzofuran-2-carboxamide, ... (5 entities in total)
• 機能のキーワード: histone acetyltransferase, small molecule inhibitor, transferase-transferase inhibitor complex, transcription, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65794.85

構造登録者

Hillig, R.C.,Puetter, V. (登録日: 2024-06-04, 公開日: 2024-11-06, 最終更新日: 2024-11-27)

主引用文献

Ter Laak, A.,Hillig, R.C.,Ferrara, S.J.,Korr, D.,Barak, N.,Lienau, P.,Herbert, S.,Fernandez-Montalvan, A.E.,Neuhaus, R.,Gorjanacz, M.,Puetter, V.,Badock, V.,Bone, W.,Strathdee, C.,Siegel, F.,Schatz, C.,Nowak-Reppel, K.,Doehr, O.,Gradl, S.,Hartung, I.V.,Meyerson, M.,Bouche, L.
Discovery and Characterization of BAY-184: A New Potent and Selective Acylsulfonamide-Benzofuran In Vivo -Active KAT6AB Inhibitor.
J.Med.Chem., 67:19282-19303, 2024

PubMed Abstract: KAT6A and KAT6B genes are two closely related lysine acetyltransferases that transfer an acetyl group from acetyl coenzyme A (AcCoA) to lysine residues of target histone substrates, hence playing a key role in chromatin regulation. KAT6A and KAT6B genes are frequently amplified in various cancer types. In breast cancer, the 8p11-p12 amplicon occurs in 12-15% of cases, resulting in elevated copy numbers and expression levels of chromatin modifiers like KAT6A. Here, we report the discovery of a new acylsulfonamide-benzofuran series as a novel structural class for KAT6A/B inhibition. These compounds were identified through high-throughput screening and subsequently optimized using molecular modeling and cocrystal structure determination. The final tool compound, BAY-184 (), was successfully validated in an proof-of-concept study.

PubMed: 39450890
DOI: 10.1021/acs.jmedchem.4c01709

実験手法

X-RAY DIFFRACTION (2.69 Å)