product name RGFP966
Description: RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM in cell-free assay, exhibits > 200-fold selectivity over other HDAC. RGFP966 is a potent HDAC3 inhibitor and has no inhibition on other HDACs at the concentration up to 15 μM. Using a substrate-dependent biochemical assay to investigate RGFP966 inhibition of HDACs, and results showed that it inhibited HDAC3 with IC50 value of 80 nM while had no effective inhibition on other HDACs. When tested with cutaneous T cell lymphoma (CTCL) cell lines with RGFP966, the cell growth were significantly decreased by inhibiting HDAC3 which increased cell apoptosis.
References: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2647-52; PLoS One. 2013 Jul 22;8(7):e68915.
362.4
Formula
C21H19FN4O
CAS No.
1357389-11-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 72 mg/mL (198.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19425057
| In Vitro |
In vitro activity: RGFP966 is a slow-on/slow-off, competitive tight-binding HDAC inhibitor, with an IC50 of 0.08μM for HDAC3 and no effective inhibition of any other HDAC at concentrations up to 15μM. RGFP966 treatment on two CTCL cell lines for 24 hours prior to western blot analysis resulted in increased acetylation at H3K9/K14, H3K27, and H4K5, but not H3K56ac. RGFP966 decreases cell growth in CTCL (cutaneous T cell lymphoma) cell lines due to increased apoptosis that is associated with DNA damage and impaired S phase progression. RGFP966 causes a significant reduction in DNA replication fork velocity within the first hour of drug treatment. Kinase Assay: Deacetylation assays are based on the homogenous fluorescence release assay. Purified recombinant enzymes are incubated with serial-diluted inhibitors at the concentrations indicated in the figures, with pre-incubation times ranging from 0 to 3 hours, in the standard HDAC buffer. Acetyl-Lys(Ac)-AMC substrate (at 10 μM, corresponding to the Km for both HDAC1 and HDAC3) is added after the pre-incubation period. The reaction is allowed to run for 1 hour. The trypsin peptidase developer, at final concentration of 5mg/ml, is added after 1 hour, and the fluorescence emission is then measured using a Tecan M200 96-well plate reader. Cell Assay: Cells are counted and split into T25 (Corning) flasks at 26105 cells/mL. Cells are then treated with DMSO, or HDIs once at hour 0. 100 ml aliquots are taken in triplicate from each flask at 0 hr, 24 hrs, 48 hrs, and 72 hrs after treatment, distributed into a flat bottom 96-well plate, and 10 ml of alamar blue added to each well. After a 4 hr incubation, fluorescence is measured using the Biotek Synergy MX Microplate Reader. |
|---|---|
| In Vivo | RGFP966 treatment (10 mg/kg) enhances long-term memory for object memory. RGFP966 (3 or 10 mg/kg, s.c.) facilitates extinction and prevents reinstatement of cocaine- conditioned place preference. |
| Animal model | Mouse |
| Formulation & Dosage | Formulated in in DMSO and diluted in a vehicle of 30% (wt/vol) hydroxypropyl-β-cyclodextrin and 100mM sodium acetate (pH 5.4); 10 mg/kg; s.c. administration. |
| References | Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2647-52; PLoS One. 2013 Jul 22;8(7):e68915. |
