RG-2833

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H25N3O2
Molecular Weight	339.4314
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)C(=O)NCCCCCC(=O)NC2=CC=CC=C2N

InChI

InChIKey=VOPDXHFYDJAYNS-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25159818 | https://www.ncbi.nlm.nih.gov/pubmed/20098685 | http://adisinsight.springer.com/drugs/800035788 | https://www.ncbi.nlm.nih.gov/pubmed/22901956

RG2833 is a compound originally developed by the Scripps Insitute for the treatment of Friedrick's Ataxia. RG2833 is a potent and selective inhibitor of neuronal histone deacetylase. RG2833 has been granted orphan drug status has been investigated in phase one clinical trials. There has also been proof of concept studies conducted for the treatment of Parkinson's disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histone deacetylase 3 35 Target ID: O15379 Gene ID: 8841.0 Gene Symbol: HDAC3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20098685	Inhibitor 8297		5.0 nM [Ki]
Histone deacetylase 1 51 Target ID: Q13547 Gene ID: 3065.0 Gene Symbol: HDAC1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20098685	Inhibitor 8297		32.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Friedreich ataxia 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25159818	Primary		Phase I 428	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22901956	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model.	2010 Jan 21	20098685
RGFP109, a histone deacetylase inhibitor attenuates L-DOPA-induced dyskinesia in the MPTP-lesioned marmoset: a proof-of-concept study.	2013 Feb	22901956
Epigenetic therapy for Friedreich ataxia.	2014 Oct	25159818

Patents

Sample Use Guides

In Vivo Use Guide

Friedrick's ataxia patients were dosed in 4 cohorts, ranging from 30mg/day to 240mg/day of the formulated drug product of HDACi 109, RG2833. Patients were monitored for adverse effects as well as for increases in frataxin mRNA, frataxin protein, and chromatin modification in blood cells. RG2833 was delivered orally in capsules containing 30mg, 60mg, or 150mg of RG2833 free base equivalents as the active pharmaceutical ingredient and Ac-Di-Sol (2% croscarmellose sodium).

Route of Administration: Oral

In Vitro Use Guide

Unstimulated peripheral blood mononuclear cells were obtained from Friedreich Ataxia patients and incubated for 48 hours with RG-28833 at 1, 2.5, 5 or 10 microM. Frataxin mRNA from cells was measured by quantitative real-time RT-PCR in RNA. RG-2833 was highly effective demonstrating up to 9-fold upregulation of frataxin mRNA production with an almost linear dose-response relationship. The increase in frataxin gene expression was paralleled by increased histone acetylation.

Name

Type

Language

RG-2833

Common Name

English

RG2833

Code

English

RG 2833 [WHO-DD]

Common Name

English

RGFP-109

Code

English

N-(6-(2-AMINOPHENYLAMINO)-6-OXOHEXYL)-4-METHYLBENZAMIDE

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/10/793