RGFP966, or RGFP-966, is a histone deacetylase (HDAC) inhibitor which is used in scientific research. It is a highly selective HDAC3 inhibitor. The drug is the most commonly used selective HDAC3 inhibitor in research.
Pharmacology Pharmacodynamics + Enzyme (nM) HDAC1 5,600–28,670 HDAC2 3,010–17,680 HDAC3 80–401 HDAC4 >20,000 HDAC5 >20,000 HDAC6 >20,000 HDAC7 >20,000 HDAC8 >100,000 HDAC9 >20,000 HDAC10 >20,000 HDAC11 >20,000 Refs:
RGFP966 is a histone deacetylase (HDAC) inhibitor, specifically acting as a highly selective HDAC3 inhibitor, with an of 80nM and no inhibition of other HDACs at concentrations of up to 15,000nM or 20,000nM.
It enhances cognition, memory, and learning in rodents. The drug reverses age-related impairments in memory updating in rodents. In addition, it has been found to facilitate the extinction of drug-seeking behavior in a manner refractory to reinstatement in rodents. Conversely, unlike the pan-class I HDAC inhibitor RGFP963, RGFP966 failed to enhance consolidation of cued fear extinction in rodents, suggesting that HDAC1 and/or HDAC2 may be involved in this instead.
Also unlike pan-class I HDAC inhibitors, which can enhance synaptogenesis, RGFP966 showed minimal effect in this regard. The drug increases brain-derived neurotrophic factor (BDNF) expression. Knockdown of HDAC2 and knockdown of HDAC3 have been found to increase BDNF expression, whereas knockdown of other HDACs did not do so.
RGFP966 produces anti-inflammatory effects. It shows antidepressant-like effects against neuroinflammation-induced depression in rodents. Similarly to butyric acid (butyrate), RGFP966 ameliorates sleep deprivation-induced intestinal mucosa-induced damage in rodents. RGFP966 has neuroprotective and neurorestorative effects in preclinical research.
Pharmacokinetics The pharmacokinetics of RGFP966 in rodents have been described. It efficiently crosses the blood–brain barrier in rodents.
History RGFP966 was first described in the scientific literature by 2013.
See also Histone deacetylase inhibitor BRD-6929 (Cpd-60) RGFP136 RGFP963
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