RGFP963

RGFP963
Clinical data
Other namesRGFP-963
Drug classHistone deacetylase inhibitor; HDAC1, HDAC2, and HDAC3 inhibitor; Cognitive enhancer
ATC code
  • None
Identifiers
  • (E)-N-(2-aminophenyl)-3-[1-[(E)-3-phenylprop-2-enyl]pyrazol-4-yl]prop-2-enamide
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC21H20N4O
Molar mass344.418 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)/C=C/CN2C=C(C=N2)/C=C/C(=O)NC3=CC=CC=C3N
  • InChI=1S/C21H20N4O/c22-19-10-4-5-11-20(19)24-21(26)13-12-18-15-23-25(16-18)14-6-9-17-7-2-1-3-8-17/h1-13,15-16H,14,22H2,(H,24,26)/b9-6+,13-12+
  • Key:KOESHVZEHKMOIK-UXKPLKHMSA-N
RGFP963 activities
EnzymeIC50Tooltip Half-maximal inhibitory concentration (nM)
HDAC11,510
HDAC2750
HDAC396
HDAC4>20,000
HDAC5>20,000
HDAC6>20,000
HDAC7>20,000
HDAC8>20,000
HDAC9>20,000
HDAC106,640–10,000
HDAC1127,700
Refs:

RGFP963, or RGFP-963, is a histone deacetylase (HDAC) inhibitor which is used in scientific research. It is a selective class I HDAC inhibitor, including of HDAC1, HDAC2, and HDAC3 (IC50Tooltip half-maximal inhibitory concentration = 1,510 nM, 750 nM, and 96 nM, respectively). The drug also weakly inhibits HDAC10 (IC50 = 6,640–10,000 nM), whereas it showed no inhibition of other HDACs at a concentration of up to 20,000 nM. RGFP963 enhances the consolidation of cued fear extinction in rodents, with this thought to be mediated by inhibition of HDAC1 and/or HDAC2 and not by inhibition of HDAC3. In addition, the drug promotes synaptogenesis in vitro and enhances memory in an animal model of Alzheimer's disease in rodents. It also enhanced cognition in a model of amyotrophic lateral sclerosis (ALS) in rodents. The pharmacokinetics of RGFP963 have been studied and it is brain-penetrant in rodents. RGFP963 was first described in the scientific literature by 2015.

See also

References

  1. 1 2 3 4 5 6 7 Bowers ME, Xia B, Carreiro S, Ressler KJ (April 2015). "The Class I HDAC inhibitor RGFP963 enhances consolidation of cued fear extinction". Learning & Memory. 22 (4). Cold Spring Harbor, N.Y.: 225–231. doi:10.1101/lm.036699.114. PMC 4371170. PMID 25776040.
  2. 1 2 3 4 5 6 Rumbaugh G, Daws SE, Ozkan ED, Rojas CS, Hubbs CR, Aceti M, et al. (September 2015). "Pharmacological Selectivity Within Class I Histone Deacetylases Predicts Effects on Synaptic Function and Memory Rescue". Neuropsychopharmacology. 40 (10): 2307–2316. doi:10.1038/npp.2015.93. PMC 4538358. PMID 25837283.
  3. 1 2 Pelaez MC, Fiore F, Larochelle N, Dabbaghizadeh A, Comaduran MF, Arbour D, et al. (September 2024). "Reversal of cognitive deficits in FUSR521G amyotrophic lateral sclerosis mice by arimoclomol and a class I histone deacetylase inhibitor independent of heat shock protein induction". Neurotherapeutics. 21 (5) e00388. doi:10.1016/j.neurot.2024.e00388. PMC 11579874. PMID 38972779.
  4. 1 2 3 Ganai SA, Ramadoss M, Mahadevan V (2016). "Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration". Current Neuropharmacology. 14 (1): 55–71. doi:10.2174/1570159x13666151021111609. PMC 4787286. PMID 26487502.
  5. ↑ "Delving into the Latest Updates on RGFP-963 with Synapse". Synapse. 7 March 2026. Retrieved 6 August 2026.
  6. ↑ Yang SS, Zhang R, Wang G, Zhang YF (2017). "The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer's disease". Translational Neurodegeneration. 6 19. doi:10.1186/s40035-017-0089-1. PMC 5504819. PMID 28702178.