ACY-738

ACY-738 is a potent, selective and orally-bioavailable HDAC6 inhibitor, with an IC₅₀ of 1.7 nM; ACY-738 also inhibits HDAC1, HDAC2, and HDAC3, with IC₅₀s of 94, 128, and 218 nM. IC50 & Target: IC50: 1.7 nM (HDAC6), 94 nM (HDAC1), 128 nM (HDAC2), 218 nM (HDAC3)^[1] In Vitro: ACY-738 (2.5?μM) increases the acetylated (lysine 40) fraction of α-tubulin in RN46A-B14 cells^[1]. ACY-738 (10 μM) induces cell death comparable to LBH589 and FK228^[3]. In Vivo: ACY-738 (5?mg/kg) leads to significant increase in α-tubulin acetylation in whole-brain lysates. ACY-738 (50?mg/kg) fails to produce an enhancement of locomotor activity in WT mice tested in a home cage environment^[1]. ACY-738 (5 mg/kg) reaches a maximum plasma concentration of 1310 ng/mL at 0.0830 h following treatment. ACY-738 (5 mg/kg BW) alters BM B cell differentiation, but shows no significant effect on IgG and C3 deposition in NZB/W mice. ACY-738 (20 mg/kg) significantly attenuates the severity of proteinuria in NZB/W F1 mice. ACY-738 (5 mg/kg) shows a significant decrease in anti-dsDNA production in NZB/W mice as they aged. ACY-738 (5, 20 mg/kg) attenuates sera IL-1β production as the NZB/W mice aged. ACY-738 (5 mg/kg) significantly reduces glomerular IL-6 and IL-10 mRNA levels by more than 50% while treatment with 20 mg/kg ACY-738 reduced IL-6 and IL-10 mRNA to non-detectable levels^[2].