Chemistry:RGFP136
RGFP136, or RGFP-136, is a histone deacetylase (HDAC) inhibitor which is used in scientific research.[1][2][3][4] It is a modestly selective or preferential HDAC3 inhibitor, with an IC50 value of 400–560 nM, whereas the drug showed 2- to 13-fold lower inhibitory potency at HDAC1 and HDAC2 (IC50 = 1,140–5,200 nM and 3,000 nM, respectively).[2][3][1][5] It shows weak inhibition of HDAC8 and no inhibition of several other HDACs, including HDAC4, HDAC5, HDAC6, and HDAC7.[5] RGFP136 has been found to enhance long-term memory in rodents, which led to conclusions that HDAC3 is a critical regulator of long-term memory formation.[2][1] It has also been found to improve symptoms in an animal model of Friedreich ataxia.[4][3] The drug's pharmacokinetics have been studied and it is brain-penetrant in rodents.[2][1] RGFP136 was first described in the scientific literature by 2011.[2][4]
See also
- Histone deacetylase inhibitor
- RGFP963
- RGFP966
References
- ↑ 1.0 1.1 1.2 1.3 "HDAC Inhibitors as Novel Therapeutics in Aging and Alzheimer's Disease". Epigenetic Regulation in the Nervous System. Elsevier. 2013. pp. 225–248. doi:10.1016/b978-0-12-391494-1.00008-2. ISBN 978-0-12-391494-1. https://linkinghub.elsevier.com/retrieve/pii/B9780123914941000082. Retrieved 31 July 2026.
- ↑ 2.0 2.1 2.2 2.3 2.4 "HDAC3 is a critical negative regulator of long-term memory formation". The Journal of Neuroscience 31 (2): 764–774. January 2011. doi:10.1523/JNEUROSCI.5052-10.2011. PMID 21228185. "RGFP136, used in these studies, has an IC50 of 5.2 μM for HDAC1, 3.0 μM for HDAC2, and 0.4 μM for HDAC3 using purified recombinant HDACs. After systemic subcutaneous injection, the maximum drug concentration (Cmax) in the brain is 1.7 μM for a 30 mg/kg dose. This suggests that, after systemic administration, as in the data shown in Figure 6, RGFP136 is at a sufficient concentration in the brain to inhibit HDAC3 but perhaps not HDAC1 or HDAC2.".
- ↑ 3.0 3.1 3.2 "Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model". PLOS ONE 5 (1). January 2010. doi:10.1371/journal.pone.0008825. PMID 20098685. Bibcode: 2010PLoSO...5.8825R.
- ↑ 4.0 4.1 4.2 "Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model". Neurobiology of Disease 42 (3): 496–505. June 2011. doi:10.1016/j.nbd.2011.02.016. PMID 21397024.
- ↑ 5.0 5.1 Cite error: Invalid
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