ACY-738 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 1.7 nM). It is selective for HDAC6 over HDAC1-3 (IC50s = 94, 128, and 218 nM, respectively). ACY-738 (5 mg/kg) increases acetylation of α-tubulin in mouse brain. It increases exploratory activity in a novel open-field test and reduces immobility time in a tail suspension test in wild-type, but not neural cell-selective HDAC6 knockout, mice when administered at a dose of 50 mg/kg, indicating anxiolytic and antidepressant-like activity, respectively. ACY-738 (100 mg/kg in the diet) attenuates decreases in caudal nerve sensory nerve action potential (SNAP) amplitude and increases in hind paw mechanical hypersensitivity in a mouse model of peripheral neuropathy induced by vincristine . It decreases hepatorenal cystogenesis in a rat model of polycystic liver disease when administered at a dose of 30 mg/kg.
