HW321005

HW321005 is a potent, selective, small-molecule inhibitor of histone lysine acetyltransferases 6A and 6B (KAT6A/6B) developed by Humanwell Healthcare. It inhibits KAT6A/6B with single-digit nanomolar IC50 values and demonstrates high selectivity over other KAT family members. In preclinical models of KAT6A-high, estrogen receptor-positive (ER+), HER2-negative breast cancer, HW321005 downregulates KAT6A-mediated histone acetylation (H3K23Ac) and estrogen receptor alpha (ERα) signaling, leading to significant dose-dependent anti-tumor efficacy. The compound possesses favorable drug-like properties, including desirable in vitro ADME characteristics, excellent in vivo exposure, low clearance, and good oral bioavailability across multiple preclinical species.