Abstract 7064: Development of a new class of KAT6A/B inhibitors with in vivo efficacy.

Abstract KAT6A and KAT6B encode lysine acetyltransferases that catalyse the transfer of acetyl groups from acetyl-CoA to lysine residues on histone proteins, thereby influencing chromatin structure and gene expression. Amplification of these genes is observed in several cancers, with the 8p11-p12 chromosomal region—containing KAT6A—being increased in copy number in approximately 12-15% of breast cancer cases, leading to higher expression of chromatin-modifying enzymes. In this study, we introduce a novel series of acylsulfonamide-benzofuran compounds that function as selective inhibitors of KAT6A and KAT6B. These inhibitors were first identified via high-throughput screening and subsequently refined through computational modelling and co-crystallization studies. The lead compound from this series, BAY-184, demonstrated efficacy in an in vivo proof-of-concept experiment, confirming its potential as a tool for targeting KAT6A/B activity. Citation Format: Antonius ter Laak, Roman Hillig, Steven Ferrara, Daniel Korr, Peter Staller, Naomi Barak, Philip Lienau, Simon Herbert, Amaury Fernandez, Roland Neuhaus, Matyas Gorjanacz, Vera Puetter, Volker Badock, Wilhelm Bone, Craig Strathdee, Franziska Siegel, Christoph Schatz, Nowak-Reppel Katrin, Olaf Doehr, Stefan Gradl, Ingo Hartung, Matthew Meyerson, Lea Bouche. Development of a new class of KAT6A/B inhibitors with in vivo efficacy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7064.