ACY-775

ACY-775 is a potent and highly selective small molecule inhibitor of histone deacetylase 6 (HDAC6). Developed by Acetylon Pharmaceuticals, it is primarily utilized in preclinical research to investigate the therapeutic potential of selective HDAC6 inhibition across various indications, including multiple myeloma and neurological disorders. Unlike pan-HDAC inhibitors or Class I-selective inhibitors, ACY-775 selectively increases the acetylation of alpha-tubulin, a non-histone substrate of HDAC6, without significantly affecting the acetylation levels of histones (H2A, H2B, H3, and H4). In studies of multiple myeloma, ACY-775 has demonstrated limited single-agent efficacy in inducing cell death compared to Class I HDAC inhibitors, suggesting that Class I inhibition is more critical for plasma cell apoptosis, although HDAC6 inhibition may be relevant in specific patient subsets or in combination with other agents.