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    RG108
    RG108

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0405
    CAS #: 48208-26-0Purity ≥98%

    Description: RG108 is a novel and potent non-nucleoside inhibitor of DNA methyltransferase ((DNMT) with IC50 of 115 nM in a cell-free assay. RG108  can enhance reprogramming of OK-transduced MEFs in the presence of BIX. RG108 caused demethylation and reactivation of tumor suppressor genes, but it did not affect the methylation of centromeric satellite sequences. These results establish RG108 will be particularly useful for the experimental modulation of epigenetic gene regulation.

    References: Cancer Res. 2005 Jul 15;65(14):6305-11; Bioconjug Chem. 2006 Mar-Apr;17(2):261-6; PLoS One. 2011;6(8):e23667. 

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    Molecular Weight (MW)334.33
    FormulaC19H14N2O4 
    CAS No.48208-26-0
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 67 mg/mL (200.4 mM)
    Water:<1 mg/mL
    Ethanol: 67 mg/mL (200.4 mM)
    Other infoChemical Name: (S)-2-(1,3-dioxoisoindolin-2-yl)-3-(1H-indol-3-yl)propanoic acid.
    InChi Key: HPTXLHAHLXOAKV-INIZCTEOSA-N
    InChi Code: InChI=1S/C19H14N2O4/c22-17-13-6-1-2-7-14(13)18(23)21(17)16(19(24)25)9-11-10-20-15-8-4-3-5-12(11)15/h1-8,10,16,20H,9H2,(H,24,25)/t16-/m0/s1
    SMILES Code: O=C(O)[[email protected]](CC1=CNC2=CC=CC=C12)N3C(C4=CC=CC=C4C3=O)=O 
    SynonymsN-Phthalyl-L-tryptophan; RG-108; RG 108; RG108; 


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    In Vitro

    In vitro activity: 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. In another study, the synthesis and in vitro analysis of a biotinylated RG108 conjugate is investigated to evaluate the interactions with DNA methyltransferase enzymes. 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.


    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. 


    Cell Assay: For the determination of cellular growth and viability, cells are stained with trypan blue and counted using a standard counting grid.

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    References

    Cancer Res. 2005 Jul 15;65(14):6305-11; Bioconjug Chem. 2006 Mar-Apr;17(2):261-6; PLoS One. 2011;6(8):e23667. 


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    RG108

    RG108
    RG108


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