Prelude Therapeutics Incorporated, 175 Innovation Boulevard, Wilmington, DE 19805, USA.
Prelude Therapeutics Incorporated, 175 Innovation Boulevard, Wilmington, DE 19805, USA.
Bioorg Med Chem Lett. 2024 Nov 15;113:129948. doi: 10.1016/j.bmcl.2024.129948. Epub 2024 Sep 3.
KAT6, a histone acetyltransferase from the MYST family, has emerged as an attractive oncology target due to its role in regulating genes that control cell cycle progression and cellular senescence. Amplification of the KAT6A gene has been seen among patients with worse clinical outcome in ER breast cancers. Although multiple inhibitors have been reported, no KAT6 inhibitors have been approved to date. Here, we report the fragment-based discovery of a series of N-(1-phenyl-1H-1,2,3-triazol-4-yl)benzenesulfonamide KAT6 inhibitors and early hit-to-lead efforts to improve the KAT6 potency.
KAT6，一种来自 MYST 家族的组蛋白乙酰转移酶，由于其在调节控制细胞周期进程和细胞衰老的基因方面的作用，已成为一个有吸引力的肿瘤学靶点。在 ER 乳腺癌患者中，已经观察到 KAT6A 基因的扩增，与更差的临床结局相关。尽管已经报道了多种抑制剂，但迄今为止没有批准的 KAT6 抑制剂。在这里，我们报告了一系列基于片段的 N-(1-苯基-1H-1,2,3-三唑-4-基)苯磺酰胺 KAT6 抑制剂的发现，以及早期的从命中发现先导化合物以提高 KAT6 效力的努力。
