RGFP966

SKU: orb1307511

Description

RGFP966 is a potent and selective HDAC3 inhibitor with an IC50 of 0.08 μM. It is widely used in research to investigate epigenetic mechanisms in neuroscience, oncology, and metabolic studies, with applications in both cellular and animal models.

Research Area

Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 1357389-11-7
• MW: 362.4
• Purity: 99.88% (May vary between batches)
• Formula: C₂₁H₁₉FN₄O
• SMILES: Nc1cc(F)ccc1NC(=O)\C=C\c1cnn(C\C=C\c2ccccc2)c1
• Target: HDAC
• Solubility: DMSO:45 mg/mL (124.17 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.52 mM)

Bioactivity

• Target IC50:
  HDAC3:80 nM(cell free)
• In Vivo:
  All mice exhibited a robust preference for the cocaine-paired context after cocaine-conditioned place preference (CPP) training. Treatment with RGFP966 (3 or 10 mg/kg, s.c.)immediately after the drug-free preference tests resulted in significant extinction of CPP on posttest 2 and posttest 3. Treatment with 10 mg/kg, but not with 3 mg/kg, resulted in a significantly rapid reduction of CPP on the subsequent days . RGFP966 at doses of 10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration, accompanied by neuroprotective effects on striatal volume .
• In Vitro:
  RGFP966 is specific for HDAC3 (IC50: 0.08 μM) and no effective inhibition of any other HDAC at concentrations up to 15 μM . In LPS/IFNγ-stimulated RAW 264.7 macrophages treatment with RGFP966 did not change the expression of the genes TNFα, iNOS, and IL-10 but provided a significant downregulation of the expression of the pro-inflammatory genes IL-1β, IL-6 and IL-12b . RGFP966 resulted in decreased cell growth in CTCL cell lines due to increased apoptosis that was associated with DNA damage and impaired S phase progression .
• Cell Research:
  To investigate the influence of the HDAC 3-selective inhibitor RGFP966 on cell viability, RAW 264.7 macrophages, HBE cells and hASM cells were seeded in 96-well plates. To obtain identical cell density at the start of the experiments, RAW 264.7 macrophages were seeded at 25,000 cells/cm2, HBE cells and hASM cells were seeded at 70% confluency (based on surface area) and were serum-starved for 24 h prior incubation with RGFP966. Shortly before incubation with RGFP966, the medium was replaced by 100 μl fresh (if appropriate serum free) culture medium. Incubations with LPS and IFNγ were performed as described for HDAC 1–3 downregulation by siRNA. After 20 h of incubation with RGFP966, 20 μl of CellTiter 96 AQueous One Solution reagent was added to each well and incubated at 37 °C for 1 h in the dark. The absorbance at 490 nm was measured using a Synergy H1 plate reader. LPS/IFNγ-stimulated cells without addition of RGFP966 were considered 100% .
• Animal Research:
  Subthreshold training and a 24-h retention test for location-dependent object recognition memory (OLM) and novel object recognition memory (ORM) were performed as described previously. Mice received an injection of RGFP966 (3, 10, or 30 mg/kg s.c) or vehicle alone either 1 h before or immediately after a 3-min training seeion .

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RGFP 966, RGFP966, RGFP-966, Inhibitor, HDAC3, HDAC, Histone deacetylases, inhibit

Compound Identifiers

PubChem CID

56650312

Rudy Matheson 1 & Kohei Chida 2 & Hui Lu 1,3 & Victoria Clendaniel 1 & Marc Fisher 4 & Ajith Thomas 5 & Eng H. Lo 6 & Magdy Selim 4 & Amjad Shehadah 4 Neuroprotective Effects of Selective Inhibition of Histone Deacetylase 3 in Experimental Stroke Ponatinib inhibitor, (2024)

PubMed: