ACY-738

Description: ACY-738 is a novel, potent, selective, brain penetrable and orally-bioavailable HDAC6 inhibitor with an IC50s of 1.7 nM; it also inhibits HDAC1, HDAC2, and HDAC3, with IC50s of 94, 128, and 218 nM. ACY-738 (2.5?uM) increases the acetylated (lysine 40) fraction of alpha-tubulin in RN46A-B14 cells. ACY-738 (10 uM) induces cell death comparable to LBH589 and FK228. ACY-738 inhibit HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs. In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity, but more limited brain bioavailability, ACY-738 induces dramatic increases in alpha-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments.

References: Neuropsychopharmacology. 2014 Jan; 39(2):389-400.Br J Haematol. 2013 Aug; 162(4):559-62.