Lysine acetyltransferase 6A and 6B (KAT6A/B)

KAT6A and KAT6B are paralogous lysine acetyltransferases belonging to the MYST family that function as the catalytic subunits of multiprotein complexes involved in chromatin remodeling and transcriptional activation [1, 4]. They primarily acetylate histone H3 at lysine 23 (H3K23ac), as well as H3K9 and H3K14, to regulate gene expression programs essential for embryonic development, hematopoiesis, and the maintenance of neural and hematopoietic stem cells [1, 12, 16]. In cancer, KAT6A is frequently amplified or overexpressed, particularly in estrogen receptor-positive (ER+) breast cancer, where it drives the expression of oncogenic factors like ESR1 and MYC [3, 5, 8]. Small-molecule inhibitors targeting the KAT6A/B acetyltransferase domain, such as prifetrastat, are designed to induce cellular senescence and cell cycle arrest in tumor cells [4, 11]. Clinical development of these inhibitors has identified dysgeusia and neutropenia as notable side effects, while H3K23ac levels serve as a key pharmacodynamic biomarker for monitoring target engagement [3, 9, 11]. These agents are currently being evaluated in clinical trials for their potential to overcome endocrine resistance in breast cancer and treat other solid tumors [6, 11].

Other names

MOZ (Monocytic Leukemia Zinc Finger Protein)MORF (MOZ-Related Factor)MYST3MYST4ZNF220RUNXBP2MOZ2QKFLysine acetyltransferase 6

Inhibition of the histone acetyltransferase (HAT) catalytic activity, specifically targeting the acetylation of histone H3 lysine 23 (H3K23ac), which leads to the suppression of oncogenic transcriptional programs (e.g., ESR1, MYC), induction of cellular senescence, and irreversible cell cycle arrest [4, 5, 8].