RG2833 (RGFP109)

Alias: RGFP 109; RGFP-109; RGFP109; RG2833; RG 2833; RG-2833
Cat No.:V0273 Purity: =98.94%
RG-2833 (formerly RGFP-109) is a potent, selective and brain-permeable inhibitor of HDAC (histone deacetylase) with potential neuroprotective effects.
RG2833 (RGFP109) Chemical Structure CAS No.: 1215493-56-3
Product category: HDAC
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Purity: =98.94%

Purity: ≥98%

Product Description

RG-2833 (formerly RGFP-109) is a potent, selective and brain-permeable inhibitor of HDAC (histone deacetylase) with potential neuroprotective effects. In cell-free assays, it inhibits HDAC1 and HDAC3 with IC50s of 60 nM and 50 nM, respectively. An experimental medication candidate called RG2833 is being researched to treat Parkinson's disease. It is being studied in phase I clinical trials after being granted orphan drug status. In an iPSC-derived neuronal cell model, FXN was upregulated and maximal deacetylase was inhibited by plasma RG2833 (5μM). The findings demonstrated a strong correlation between the downregulation of deacetylase activity and the increase in FXN (Friedreich Ataxia) transcript, indicating that deacetylation is the mechanism of action of RG2833.

Biological Activity I Assay Protocols (From Reference)
Targets
HDAC3 ( IC50 = 50 nM ); HDAC1 ( IC50 = 60 nM ); HDAC1 ( Ki = 32 nM ); HDAC3 ( Ki = 5 nM )
ln Vitro
In vitro activity: RG2833's Ki values for HDAC1 and HDAC3 are 32 nM and 5 nM, in that order. RG2833 demonstrates high activity throughout the entire tested concentration range of 1 to 10 µM. Frataxin protein increases more slowly in cells from patient P13 when RG2833 is continuously cultivated, but it increases quickly in the cells after the compound is removed[1]. In addition to reducing neuronal pathology of the dorsal root ganglia (DRG), RG2833 causes notable increases in brain aconitase enzyme activity[2].

ln vivo
RG2833 (150 mg/kg) is capable of treating KIKI mice's brain and heart frataxin deficiency 24 hours after a single injection, but not at lower doses. When tracked over time, the KIKI mouse's increased levels of frataxin mRNA caused by RG2833 can be seen in the brain and heart at 12 hours and 24 hours, respectively[1]. After a chronic dosage of 100 mg/kg, s.c., mice tolerate RG2833 well and do not experience any toxicity. RG2833 enhances YG8R FRDA mice's motor coordination. In the brains of YG8R FRDA mice, RG2833 increases the expression of the frataxin protein[2]. After a single or six-day once-daily treatment, RGFP109 (30 mg/kg, p.o. once daily for six days) has no acute effects on dyskinesia. Dyskinesia and the amount of time spent ON-time with incapacitating dyskinesia are reduced by 37% and 50%, respectively, one week after RGFP109 is stopped[3].
Enzyme Assay
Aconitase activities are measured by centrifuging mouse brain tissues at 800×g for 10 min at 4°C after homogenizing them on ice at 10% w/v in CellLytic MT Mammalian Tissue Lysis/Extraction buffer. After adding 50 μL of tissue lysates to 200 μL of substrate mix (which included 50 mM Tris/HCl pH7.4, 0.4 mM NADP, 5 mM Na citrate, 0.6 mM MgCl2, 0.1% (v/v) Triton X-100, and 1U isocitrate dehydrogenase), the reactions were incubated for 15 minutes at 37°C.The reaction slope was then determined by taking spectrophotometric absorbance measurements every minute for 15 minutes at 340 nm 37°C. Afterwards, using a citrate synthase assay kit, the aconitase activities of mouse brain tissues are normalized to citrate synthase activities.
Cell Assay
RG2833's Ki values for HDAC1 and HDAC3 are 5.4 nM and 7.8 nM, in that order. RG2833 demonstrates high activity throughout the entire tested concentration range of 1 to 10 µM. Frataxin protein increases more slowly in cells from patient P13 when RG2833 is continuously cultivated; however, upon removal of the compound, frataxin protein levels rose quickly. In addition to reducing neuronal pathology in the dorsal root ganglia (DRG), RG2833 causes notable increases in brain aconitase enzyme activity.
Animal Protocol
Mice are kept in standard open cages with 13 hours of light, 11 hours of darkness, 20–23°C, 45–60% humidity, Litaspen Premium 8/20 bedding, paper wool nesting, and standard fun tunnel environmental enrichment. SDS RM3 Expanded food pellets and regular drinking water are fed to the mice. The mice are subcutaneously injected with 150 mg/kg RG2833 three times a week for 4.5 months, or 50 mg/kg 136 or 100 mg/kg RG2833 five times a week for five months. Twenty-four hours after the last injection, the mice are culled in order to collect tissue.
References

[1]. Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model. PLoS One. 2010, 5(1), e8825.

[2]. Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model. Neurobiol Dis. 2011, 42(3), 496-505.

[3]. RGFP109, a histone deacetylase inhibitor attenuates L-DOPA-induced dyskinesia in the MPTP-lesioned marmoset: a proof-of-concept study. Parkinsonism Relat Disord. 2013, 19(2), 260-264.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H25N3O2
Molecular Weight
339.43
Exact Mass
339.19
Elemental Analysis
C, 70.77; H, 7.42; N, 12.38; O, 9.43
CAS #
1215493-56-3
Appearance
Solid powder
SMILES
CC1=CC=C(C=C1)C(=O)NCCCCCC(=O)NC2=CC=CC=C2N
InChi Key
VOPDXHFYDJAYNS-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H25N3O2/c1-15-10-12-16(13-11-15)20(25)22-14-6-2-3-9-19(24)23-18-8-5-4-7-17(18)21/h4-5,7-8,10-13H,2-3,6,9,14,21H2,1H3,(H,22,25)(H,23,24)
Chemical Name
N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide
Synonyms
RGFP 109; RGFP-109; RGFP109; RG2833; RG 2833; RG-2833
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~68 mg/mL (~200.3 mM)
Water: <1 mg/mL
Ethanol: ~10 mg/mL (~29.6 mM)
Solubility (In Vivo)
5%DMSO Corn oil: 6.0mg/ml (17.68mM) (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.9461 mL 14.7306 mL 29.4612 mL
5 mM 0.5892 mL 2.9461 mL 5.8922 mL
10 mM 0.2946 mL 1.4731 mL 2.9461 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Biological Data
  • RG2833 (RGFP109)
    Structure and kinetic properties of histone deacetylase inhibitors. Compound 109 is RG2833).PLoS One.2010 Jan 21;5(1):e8825.
    RG2833 (RGFP109)
    Effect of compounds 106, 109 and 136 in unstimulated KIKI splenocytes.
  • RG2833 (RGFP109)
    Time course for drug exposure, frataxin mRNA expression, and histone acetylation changes in the brain and heart of KIKI mice.
    RG2833 (RGFP109)
    Effect of compounds 136 and 109 on FRDA patients primary lymphocytes.PLoS One.2010 Jan 21;5(1):e8825.
  • RG2833 (RGFP109)
    Frataxin expression changes as function of drug 136 dosage.PLoS One.2010 Jan 21;5(1):e8825.
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