RGFP966
Inhibitor of HDAC3
Structure
In Cells
In Model Organisms
SERP ratings and comments
SERP Ratings
(last updated: 26 Apr 2017 )
SERP Ratings
SERP Comments:
This is an N-(o-amino-phenyl)carboxamide HDAC3-selective inhibitor with an IC50 of 80 nM and 'no effective inhibition of other HDACs' at concentrations up to 15 uM utilizing a substrate-dependent biochemical assay with recombinant human protein (Malvaez et al PNAS 2013; 110: 2647-2652 - primary data not shown). However, functional data suggests possible inhibition of other class I HDACs at concentrations >1 uM (Matthews et al Blood 2015; 126: 2392-2403) - please refer to 'cellular concentration notes'. For in vivo dosing, 10 mg/kg delivered subcutaneously achieves a maximum tissue concentration (brain) in mice of 3.15 uM at 30 minutes, with concentrations exceeding the IC50 for HDAC3 for at least 2 hours in this tissue.
(last updated: 31 May 2017 )
SERP Ratings
SERP Comments:
RGFP966 has been demonstrated to have selective activity for HDAC3 in biochemical assays over most other HDAC enzymes. In cells, Matthews et al., (Blood, 2015) observed that RGFP966 treatment phenocopied genetic HDAC3 perturbation up to ~1,000 nM. Thus, cellular studies using RGFP966 for selective pharmacologic HDAC3 perturbation should be limited to concentrations <1,000 nM. In mouse and rat models, RGFP966 has been observed to be brain-penetrant when dosed subcutaneously. When used for in vivo studies, care should be taken to pair phenotypic observations from genetic-perturbation studies of HDACs in order to have higher confidence in HDAC3-selective effects.
(last updated: 12 Jun 2017 )
Portal Comments
According to the latest paper from Olsen’s Lab (DOI:10.1021/acsmedchemlett.1c00702) RGFP966 has only a marginal preference for HDAC3 vs HDAC1 and 2, hence it shouldn’t be considered as a selective probe for HDAC3.
(last updated: 25 May 2022)