RGFP966

RGFP966 is a highly selective HDAC3 inhibitor with an IC₅₀ of 80 nM and shows no inhibition to other HDACs at concentrations up to 15 μM. RGFP966 can penetrate the blood brain barrier (BBB). IC50 & Target:IC50: 80 nM (HDAC3)^[1] In Vitro: RGFP966 potently and selectively inhibits HDAC 3 with IC₅₀ of 0.21 μM in RAW 264.7 macrophages, while HDACs 1 (IC₅₀=5.6 μM), 2 (9.7 μM) and 8 (>100 μM), indicating a good level of selectivity for HDAC 3. The mRNA levels of HDACs 1, 2 and 3 are not significantly affected by RGFP966 in RAW 264.7 macrophages, whereas the HDAC 1 and HDAC 2 protein levels are slightly, though significantly, reduced upon RGFP966 treatment. Moreover, RGFP966 significantly reduced the transcriptional activity of NF-κB p65, whereas NF-κB p65 acetylation and localization remain unaltered^[2]. In Vivo: RGFP966 (10 and 25 mg/kg) treatment significantly improves body weight, rotarod performance and several measures of motor function in the open field locomoter test^[3]. RGFP966 at a 10 mg/kg dose penetrates the blood-brain barrier into rat auditory cortex with typical pharmacokinetics, which together establish feasibility for the modulation of A1 plasticity due to action in the auditory cortex^[4].