RG108

Names

[ Name ]:
RG108

[Synonym ]:
DNA Methyltransferase Inhibitor
N-phthalimide l-tryptophane
1H-Indole-3-propanoic acid, α-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-, (αS)-
N-Phthalyl-L-tryptophan
(2S)-2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid
N-Phth-Trp-OH
RG108

Biological Activity

[Description]:

RG108 is a non-nucleoside inhibitor of DNA methyltransferase with an IC50 of 115 nM.

[Related Catalog]:

Signaling Pathways >> Epigenetics >> DNA Methyltransferase

Research Areas >> Cancer

[Target]

CpG methylase M.SssI:115 nM (IC50)

[In Vitro]

RG108 effectively blocks DNA methyltransferases in vitro and does not cause covalent enzyme trapping in human cell lines. Incubation of cells with low micromolar concentrations of RG108 results in significant demethylation of genomic DNA without any detectable toxicity. Intriguingly, RG108 causes demethylation and reactivation of tumor suppressor genes, but it does not affect the methylation of centromeric satellite sequences[1]. In another study, the synthesis and in vitro analysis of a biotinylated RG108 conjugate is investigated to evaluate the interactions with DNA methyltransferase enzymes[2]. In a recent study, it is shown RG108 can significantly reduce the DNA methyltransferases activity in SM derived iPS cells as compared to the native SMs[3].

[Kinase Assay]

The substrate DNA for the in vitro methylation assay is a 798 bp fragment (−423/+375 relative to the initiation codon) from the promoter region of the human p16Ink4a gene. The methylation reaction contains 350 to 400 ng substrate DNA and 4 units of M.SssI methylase (0.5 μM) in a final volume of 50 μL. Inhibitors are added to final concentrations of 10, 100, 200, and 500 μM, respectively. Reactions are done at 37°C for 2 hours. After completion, the reaction is inactivated at 65°C for 15 minutes and the DNA is purified using PCR Purification kit. Three hundred nanograms of purified DNA is digested for 3 hours at 60°C with 30 units of BstUI and analyzed on 2% Tris-borate EDTA agarose gels.

[References]

[1]. Brueckner B, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 2005 Jul 15;65(14):6305-11.

[2]. Schirrmacher E, et al. Synthesis and in vitro evaluation of biotinylated RG108: a high affinity compound for studying binding interactions with human DNA methyltransferases. Bioconjug Chem. 2006 Mar-Apr;17(2):261-6.

[3]. Pasha Z, et al. Efficient non-viral reprogramming of myoblasts to stemness with a single small molecule to generate cardiac progenitor cells. PLoS One. 2011;6(8):e23667.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
606.0±50.0 °C at 760 mmHg

[ Melting Point ]:
192-194℃

[ Molecular Formula ]:
C₁₉H₁₄N₂O₄

[ Molecular Weight ]:
334.326

[ Flash Point ]:
320.3±30.1 °C

[ Exact Mass ]:
334.095367

[ PSA ]:
90.47000

[ LogP ]:
3.33

[ Appearance of Characters ]:
yellow

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.741

[ Storage condition ]:
Store at RT

[ Water Solubility ]:
DMSO: >10mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

Inhibition of DNA methyltransferase as a novel therapeutic strategy to overcome acquired resistance to dual PI3K/mTOR inhibitors.

Oncotarget 6(7) , 5134-46, (2015)

Dual PI3K/mTOR(phosphatidylinositol 3-kinase/mammalian target of rapamycin) inhibitors are being evaluated clinically for the treatment of tumors with a hyperactivated PI3K/mTOR pathway. However, unex...

c-ETS transcription factors play an essential role in the licensing of human MCM4 origin of replication.

Biochim. Biophys. Acta 1849 , 1319-28, (2015)

In metazoans, DNA replication is a highly regulated and ordered process that occurs during the S phase of cell cycle. It begins with the licensing of origins of replication usually found in close prox...

DNA methyltransferase DNMT3A associates with viral proteins and impacts HSV-1 infection.

Proteomics 15 , 1968-82, (2015)

Viral infections can alter the cellular epigenetic landscape, through modulation of either DNA methylation profiles or chromatin remodeling enzymes and histone modifications. These changes can act to ...