RGFP963

RGFP963 is a potent and selective small molecule inhibitor of class I histone deacetylases (HDACs), specifically targeting HDAC1, HDAC2, and HDAC3. It exhibits IC50 values of 1.51 μM for HDAC1, 0.75 μM for HDAC2, and 0.096 μM for HDAC3[2]. The compound shows weak inhibition of HDAC10 and does not significantly inhibit other HDAC isoforms[2]. RGFP963 is able to cross the blood-brain barrier and has demonstrated activity in enhancing consolidation of cued fear extinction as well as improving cognitive function in animal models relevant to neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS)[1][2]. Its mechanism involves epigenetic modulation through inhibition of class I histone deacetylases, leading to changes in gene expression associated with learning, memory consolidation, synaptic efficacy enhancement, and potential neuroprotection[1][2].