RG2833(RGFP109) - 半岛电竞官方网址

Molecular Weight (MW)	339.43
Formula	C20H25N3O2
CAS No.	1215493-56-3
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility(In vitro)	DMSO: 68 mg/mL (200.3 mM)
Water: <1 mg/mL
Ethanol: 10 mg/mL (29.6 mM)
SMILES	O=C(NCCCCCC(NC1=CC=CC=C1N)=O)C2=CC=C(C)C=C2
Synonyms	RGFP 109; RGFP-109; RGFP109; RG2833; RG 2833; RG-2833 Chemical Name: N-(6-(2-Aminophenylamino)-6-oxohexyl)-4-methylbenzamide SMILES Code: O=C(NCCCCCC(NC1=CC=CC=C1N)=O)C2=CC=C(C)C=C2

Molecular Weight (MW)

339.43

Formula

C20H25N3O2

CAS No.

1215493-56-3

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility(In vitro)

DMSO: 68 mg/mL (200.3 mM)

Water: <1 mg/mL

Ethanol: 10 mg/mL (29.6 mM)

SMILES

O=C(NCCCCCC(NC1=CC=CC=C1N)=O)C2=CC=C(C)C=C2

Synonyms

RGFP 109; RGFP-109; RGFP109; RG2833; RG 2833; RG-2833

Chemical Name: N-(6-(2-Aminophenylamino)-6-oxohexyl)-4-methylbenzamide

SMILES Code: O=C(NCCCCCC(NC1=CC=CC=C1N)=O)C2=CC=C(C)C=C2

In Vitro	In vitro activity: RGFP109 dose-dependently upregulates frataxin mRNA and protein levels in cultures of unstimulated peripheral blood mononuclear cells (PBMC) obtained from FRDA patients. Kinase Assay: Aconitase activities are determined by homogenization of mouse brain tissues on ice at 10% w/v in CellLytic MT Mammalian Tissue Lysis/Extraction buffer, followed by centrifugation at 800×g for 10 min at 4°C. Tissue lysates (50 μL) are then added to 200 μL of substrate mix (50 mM Tris/HCl pH 7.4, 0.4 mM NADP, 5 mM Na citrate, 0.6 mM MgCl2, 0.1% (v/v) Triton X-100 and 1U isocitrate dehydrogenase) and the reactions are incubated at 37°C for 15 min, followed by spectrophotometric absorbance measurements every minute for 15 min at 340 nm 37°C to determine the reaction slope. Aconitase activities of mouse brain tissues are then normalized to citrate synthase activities, which are determined using a citrate synthase assay kit. Cell Assay:The Ki values of RG2833 for HDAC1 and HDAC3 are 5.4 nM and 7.8 nM, respectively. RG2833 is highly active in the whole tested concentration range from 1 to 10 μM. Continuous incubation with RG2833 slows the increase in frataxin protein, and when the compound is removed, frataxin protein levels rapidly increased in the cells from patient P13. RG2833 produces significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG).
In Vivo	RG2833 (150 mg/kg) corrects frataxin deficiency and increases histone acetylation in the brain and heart of KIKI mice without acute toxicity signs. RGFP109 ameliorates the disease phenotype of a Friedreich ataxia mouse model. RGFP109 (30 mg/kg p.o.) also alleviates established l-DOPA-induced dyskinesia.
Animal model	Mice are housed in conventional open cages with Litaspen Premium 8/20 bedding, paper wool nesting and standard fun tunnel environmental enrichment, with 13 h light, 11 h dark, 20-23°C and 45-60% humidity. The mice are given a diet of SDS RM3 Expanded food pellets and standard drinking water. Mice are given subcutaneous injections of 150 mg/kg RG2833 three times per week for 4.5 months, or 50 mg/kg 136 or 100 mg/kg RG2833 five times per week for 5 months, followed by culling for tissue collection 24 h after the final injection.
Formulation & Dosage	Formulated in a vehicle solution of 20% glycerol, 20% PEG400, 20% propylene glycol, 5 mM Na acetate pH 5.2.; s.c. administration.
References	PLoS One. 2010 Jan 21;5(1):e8825; Neurobiol Dis. 2011 Jun;42(3):496-505; Parkinsonism Relat Disord. 2013 Feb;19(2):260-4.

In Vitro

In vitro activity: RGFP109 dose-dependently upregulates frataxin mRNA and protein levels in cultures of unstimulated peripheral blood mononuclear cells (PBMC) obtained from FRDA patients.

Kinase Assay: Aconitase activities are determined by homogenization of mouse brain tissues on ice at 10% w/v in CellLytic MT Mammalian Tissue Lysis/Extraction buffer, followed by centrifugation at 800×g for 10 min at 4°C. Tissue lysates (50 μL) are then added to 200 μL of substrate mix (50 mM Tris/HCl pH 7.4, 0.4 mM NADP, 5 mM Na citrate, 0.6 mM MgCl2, 0.1% (v/v) Triton X-100 and 1U isocitrate dehydrogenase) and the reactions are incubated at 37°C for 15 min, followed by spectrophotometric absorbance measurements every minute for 15 min at 340 nm 37°C to determine the reaction slope. Aconitase activities of mouse brain tissues are then normalized to citrate synthase activities, which are determined using a citrate synthase assay kit.

Cell Assay:The Ki values of RG2833 for HDAC1 and HDAC3 are 5.4 nM and 7.8 nM, respectively. RG2833 is highly active in the whole tested concentration range from 1 to 10 μM. Continuous incubation with RG2833 slows the increase in frataxin protein, and when the compound is removed, frataxin protein levels rapidly increased in the cells from patient P13. RG2833 produces significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG).

In Vivo

RG2833 (150 mg/kg) corrects frataxin deficiency and increases histone acetylation in the brain and heart of KIKI mice without acute toxicity signs. RGFP109 ameliorates the disease phenotype of a Friedreich ataxia mouse model. RGFP109 (30 mg/kg p.o.) also alleviates established l-DOPA-induced dyskinesia.

Animal model

Mice are housed in conventional open cages with Litaspen Premium 8/20 bedding, paper wool nesting and standard fun tunnel environmental enrichment, with 13 h light, 11 h dark, 20-23°C and 45-60% humidity. The mice are given a diet of SDS RM3 Expanded food pellets and standard drinking water. Mice are given subcutaneous injections of 150 mg/kg RG2833 three times per week for 4.5 months, or 50 mg/kg 136 or 100 mg/kg RG2833 five times per week for 5 months, followed by culling for tissue collection 24 h after the final injection.

Formulation & Dosage

Formulated in a vehicle solution of 20% glycerol, 20% PEG400, 20% propylene glycol, 5 mM Na acetate pH 5.2.; s.c. administration.

References

PLoS One. 2010 Jan 21;5(1):e8825; Neurobiol Dis. 2011 Jun;42(3):496-505; Parkinsonism Relat Disord. 2013 Feb;19(2):260-4.

CAS NO:	1215493-56-3
规格:	≥98%

包装	价格(元)
1mg	电议
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议
1g	电议