RGFP136

RGFP136
Clinical data
Other namesRGFP-136; Repligen-136; "Compound 136"
Drug classHistone deacetylase inhibitor; HDAC3 inhibitor; Cognitive enhancer
ATC code
  • None
Identifiers
  • N-[6-(2-amino-4-fluoroanilino)-6-oxohexyl]-4-methylbenzamide
PubChem CID
ChemSpider
ChEBI
ChEMBL
Chemical and physical data
FormulaC20H24FN3O2
Molar mass357.429 g·mol−1
3D model (JSmol)
  • CC1=CC=C(C=C1)C(=O)NCCCCCC(=O)NC2=C(C=C(C=C2)F)N
  • InChI=1S/C20H24FN3O2/c1-14-6-8-15(9-7-14)20(26)23-12-4-2-3-5-19(25)24-18-11-10-16(21)13-17(18)22/h6-11,13H,2-5,12,22H2,1H3,(H,23,26)(H,24,25)
  • Key:BEFOBMGNAJJGSD-UHFFFAOYSA-N
RGFP136 activities
EnzymeIC50Tooltip Half-maximal inhibitory concentration (nM)
HDAC11,140–5,200
HDAC23,000
HDAC3400–560
HDAC4>180,000
HDAC5>180,000
HDAC6>180,000
HDAC7>180,000
HDAC813,200
HDAC9ND
HDAC10ND
HDAC11ND
Refs:

RGFP136, or RGFP-136, is a histone deacetylase (HDAC) inhibitor which is used in scientific research. It is a modestly selective or preferential HDAC3 inhibitor, with an IC50Tooltip half-maximal inhibitory concentration 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). It shows weak inhibition of HDAC8 and no inhibition of several other HDACs, including HDAC4, HDAC5, HDAC6, and HDAC7. 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. It has also been found to improve symptoms in an animal model of Friedreich ataxia. The drug's pharmacokinetics have been studied and it is brain-penetrant in rodents. RGFP136 was first described in the scientific literature by 2011.

See also

References

  1. 1 2 3 4 5 6 McQuown SC, Barrett RM, Matheos DP, Post RJ, Rogge GA, Alenghat T, et al. (January 2011). "HDAC3 is a critical negative regulator of long-term memory formation". The Journal of Neuroscience. 31 (2): 764–774. doi:10.1523/JNEUROSCI.5052-10.2011. PMC 3160172. 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.
  2. 1 2 3 4 Rai M, Soragni E, Chou CJ, Barnes G, Jones S, Rusche JR, et al. (January 2010). "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) e8825. Bibcode:2010PLoSO...5.8825R. doi:10.1371/journal.pone.0008825. PMC 2809102. PMID 20098685.
  3. 1 2 3 4 5 Nott A, Fass DM, Haggarty SJ, Tsai LH (2013). "HDAC Inhibitors as Novel Therapeutics in Aging and Alzheimer's Disease". Epigenetic Regulation in the Nervous System. Elsevier. pp. 225–248. doi:10.1016/b978-0-12-391494-1.00008-2. ISBN 978-0-12-391494-1. Retrieved 31 July 2026.
  4. 1 2 3 Abdallah DI, de Araujo ED, Patel NH, Hasan LS, Moriggl R, Krämer OH, et al. (2023). "Medicinal chemistry advances in targeting class I histone deacetylases" (PDF). Exploration of Targeted Anti-Tumor Therapy. 4 (4): 757–779. doi:10.37349/etat.2023.00166. PMC 10497394. PMID 37711592.
  5. 1 2 3 Sandi C, Pinto RM, Al-Mahdawi S, Ezzatizadeh V, Barnes G, Jones S, et al. (June 2011). "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. doi:10.1016/j.nbd.2011.02.016. PMC 3107941. PMID 21397024.