ACY-738

**ACY-738** is a potent and selective small molecule inhibitor of histone deacetylase 6 (**HDAC6**) with an IC50 of 1.7 nM, demonstrating 50- to 150-fold selectivity over class I HDACs (HDAC1-3, IC50s 94-218 nM). Originally developed by **Acetylon Pharmaceuticals** (later acquired by Celgene), it increases α-tubulin acetylation without significantly affecting histone acetylation, thereby stabilizing microtubules, enhancing axonal transport, and promoting neuroprotection. It has shown preclinical efficacy in models of neurodegenerative diseases (e.g., ALS, Alzheimer's, Krabbe disease), multiple sclerosis, depression, and systemic lupus erythematosus (SLE), with rapid brain penetration despite a short plasma half-life (~12 min).[1][2][3][4][5][7][9][10]

Other names

N-hydroxy-2-(1-phenylcycloproylamino)pyrimidine-5-carboxamide