ACY-1035

ACY-1035 is an orally bioavailable, small-molecule histone deacetylase (HDAC) inhibitor belonging to the biaryl aminobenzamide class, designed to selectively inhibit class I HDAC isoforms 1 and 2 over HDAC3 and other HDACs. In biochemical assays, ACY-1035 shows low-nanomolar inhibitory potency against HDAC1 and HDAC2, with more than 150-fold selectivity versus HDAC3 and no detectable inhibition of HDAC4–9 at concentrations up to 20 μM, leading to increased acetylation of histone residues such as H2BK5 and H3K56 in acute myeloid leukemia (AML) cells.[1][3] In preclinical AML models, ACY-1035 reduces cell viability at micromolar concentrations, induces myeloid differentiation, causes cell-cycle arrest, and promotes apoptosis, and it has been studied in combination with azacitidine to explore synergistic epigenetic antileukemic effects.[1]