RG 108
RG108 is a DNA methyltransferase (DMNT) inhibitor that enhanced reprogramming of OK-transduced MEFs in the presence of BIX. It is a small molecule that effectively blocked DNA methyltransferases in vitro and did not cause covalent enzyme trapping in human cell lines. DNA methylation regulates gene expression in normal and malignant cells. DNA methyltransferase inhibitors are able to reactivate epigenetically silenced genes. RG108 caused demethylation and reactivation of tumor suppressor genes, but it did not affect the methylation of centromeric satellite sequences. These results establish RG108 as a DNA methyltransferase inhibitor with fundamentally novel characteristics that will be particularly useful for the experimental modulation of epigenetic gene regulation.
References
Yan Shi, Caroline Desponts, Jeong Tae Do, Heung Sik Hahm, Hans R. Sch?ler, Sheng Ding. Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Oct4 and Klf4 with Small-Molecule Compounds. Cell Stem Cell. 2008; 3(5): 568 – 574.
Bodo Brueckner, Regine Garcia Boy, Pawel Siedlecki. Epigenetic Reactivation of Tumor Suppressor Genes by a Novel Small-Molecule Inhibitor of Human DNA Methyltransferases. Cancer Research. 2005; 65(14): 6305 – 11.
- 1. Zhang B, Wang W, et al. "Inositol polyphosphate-4-phosphatase type II plays critical roles in the modulation of cadherin-mediated adhesion dynamics of pancreatic ductal adenocarcinomas." Cell Adh Migr. 2018 Aug 19:1-16. PMID:29952716
- 2. Stenzig J, Schneeberger Y, et al. "Pharmacological inhibition of DNA methylation attenuates pressure overload-induced cardiac hypertrophy in rats." J Mol Cell Cardiol. 2018 May 21;120:53-63. PMID:29792884
- 3. Schneeberger, Yvonne, et al. "Pharmacokinetics of the Experimental Non‐Nucleosidic DNA Methyl Transferase Inhibitor N‐Phthalyl‐L‐Tryptophan (RG 108) in Rats." Basic & clinical pharmacology & toxicology (2015). PMID:26525153
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 334.33 |
| Cas No. | 48208-26-0 |
| Formula | C19H14N2O4 |
| Synonyms | N-Phthalyl-L-tryptophan,RG108 |
| Solubility | insoluble in H2O; ≥16.7 mg/mL in DMSO; ≥45.9 mg/mL in EtOH |
| Chemical Name | (2S)-2-(1,3-dioxoisoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid |
| SDF | Download SDF |
| Canonical SMILES | C1=CC=C2C(=C1)C(=O)N(C2=O)C(CC3=CNC4=CC=CC=C43)C(=O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
The human promyelocytic leukemia HL-60 cells. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
48 h; 50 μM |
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Applications |
Cells were pretreated with 50 μM RG108 for 48 h and then after removal of the inhibitor cultivated with 1 μM RA for the next 4 days. Viable cell number was determined daily by counting in a hemocytometer after staining with 0.2% trypan blue. Cell cycle analysis of PI stained cells by flow cytometry demonstrated a slight decrease in the proportion of cells in S-phase (by 20% from control) after treatment with minor changes in G2/M. |
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Other notes |
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References: [1] Savickiene J, Treigyte G, Borutinskaite V V, et al. Antileukemic activity of combined epigenetic agents, DNMT inhibitors zebularine and RG108 with HDAC inhibitors, against promyelocytic leukemia HL-60 cells[J]. Cellular & molecular biology letters, 2012, 17(4): 501-525. |
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| Description | RG 108 is a small-molecule inhibitor of DNMT(DNA methyltransferases) with an IC50 values of 600 nM in M.SssI assay. | |||||
| Targets | DNMT | |||||
| IC50 | 600 nM | |||||
Quality Control & MSDS
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