|Chemical Name||2-Propenamide, N-(2-amino-4-fluorophenyl)-3-[1-[(2E)-3-phenyl-2-propen-1-yl]-1H-pyrazol-4-yl]-, (2E)-|
|Solubility (25°C) *||In vitro||DMSO||72 mg/mL (198.67 mM)|
|In vivo||2% DMSO+30% PEG 300+5% Tween 80+ddH2O||5mg/mL|
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
|Description||RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM in cell-free assay, exhibits > 200-fold selectivity over other HDAC.|
|In vitro||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. |
|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. |
|Deacetylation assays||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 lines||HH and Hut78 CTCL cell lines|
|Incubation Time||24 to 72 h|
|Method||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.|
|Formulation||dissolved in DMSO and diluted in a vehicle of 30% (wt/vol) hydroxypropyl-β-cyclodextrin and 100mM sodium acetate (pH 5.4).|
|Dosages||10 mg/kg, 10.0 mL/kg|
Data from [Data independently produced by , , Front Mol Neurosci, 2016, 9:131]
Representative images of Fluoro-Jade C staining in each group. The histogram shows the numbers of degenerating neurons in the cortex 24 h (C) or 7 days (D) after MCAO (over 30 slices from five rats per group). ∗∗p < 0.01, ∗∗∗p < 0.001 versus MCAO group, ANOVA. Functional outcomes were assessed using the neurological deficits score (day 1, 4, and 7 after MCAO)
Data from [Data independently produced by , , J Immunol, 2015, 195(11):5421-31]
BMDC were stimulated for 7 h with LPS plus SAHA (4 μM), M344 (0.5 μM), TSA (100 nM), PCI-34051 (10 μM), valproate (Val; 5 mM), PD106 (10 μM), MS-275 (5 μM), sirtuin inhibitor (10 μM), RGFP966 (10 μM), MC1568 (10 μM), droxinostat (drox; 10 μM), CAY10603 (500 nM), or sodium butyrate (butyrate) (5 mM). (D) IL-1β concentrations were determined in the supernatants by ELISA.
Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response [Long J, et al. Leukemia, 2017, 31(12):2761-2770]PubMed: 28462918
Regulation of the glycerol transporter, aquaporin-3, by histone deacetylase-3 and p53 in keratinocytes [Choudhary V, et al. J Invest Dermatol, 2017, 137(9):1935-1944]PubMed: 28526298
Inhibition of Histone Deacetylases Permits Lipopolysaccharide-Mediated Secretion of Bioactive IL-1β via a Caspase-1-Independent Mechanism. [Stammler D, et al. J Immunol, 2015, 195(11):5421-31]PubMed: 26519528
MAPK signaling pathways and HDAC3 activity are disrupted during differentiation of emerin-null myogenic progenitor cells [Collins CM, et al. Dis Model Mech, 2017, 10(4):385-397]PubMed: 28188262
The histone deacetylase inhibitor valproic acid inhibits NKG2D expression in natural killer cells through suppression of STAT3 and HDAC3 [Ni L, et al. Sci Rep, 2017, 7:45266]PubMed: 28338101
Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway [Yun T, et al. J Biol Chem, 2016, 291(14):7386-95]PubMed: 26851285
HDAC3-selective inhibition activates brown and beige fat through PRDM16 [Liao J, et al. Endocrinology, 2018, 159(7):2520-2527]PubMed: 29757434
HDAC1/2‐mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF‐α [Romanick SS, et al. J Cell Physiol, 2018, 10.1002/jcp.27265]PubMed: 30203485
Inhibition of Histone Deacetylase 3 (HDAC3) Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats. [Yang X, et al. Front Mol Neurosci, 2016, 9:131]PubMed: 27965534
Validation of histone deacetylase 3 as a therapeutic target in castration-resistant prostate cancer [McLeod AB, et al. Prostate, 2018, 78(4):266-277]PubMed: 29243324
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