RG108 is a non-nucleoside DNA methyltransferase (DMNT) inhibitor. RG108 effectively blocked DNA methyltransferases in vitro and did not cause covalent enzyme trapping in human cell lines. RG108 also inhibits human tumor cell line (HCT116, NALM-6) proliferation and increased doubling time in culture. RG108 significantly reduces the methylation of genomic DNA in cells at 10 μM without detectable toxicity, distinguishing it from nucleoside-based inhibitors like 5-azacytidine. Through these actions, RG108 demethylates and reactivates epigenetically silenced tumor suppressor genes.
|Cell lines||HCT116 (left) and NALM-6 cells|
|Preparation method||Cell culture. NALM-6 ( 25) and HCT116 ( 26) cells were cultured under standard conditions in RPMI 1640 and McCoy's 5a medium, respectively. To analyze the effect of DNA methyltransferase inhibitors, cells were cultivated in media supplemented with 5-azacytidine, RG108, or RG119, as indicated. Unless stated otherwise, cells were harvested after 96 hours for further analysis. For the determination of cellular growth and viability, cells were stained with trypan blue and counted using a standard counting grid.|
|Incubation time||5 days|
|Animal models||rat model of post kainic acid-induced epilepsy|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 50 mg/mL
Ethanol 50 mg/mL
|Source||Eur Rev Med Pharmacol Sci (2017). Figure 2. RG108|
|Cell Lines||Ishikawa Cell|
|Concentrations||5 μM, 10 μM, 20 μM, 40 μM|
|Incubation Time||72 h|
|Results||The proportion of cells in G2/M phase was gradually increased with the time|
Synthesis and in vitro evaluation of biotinylated RG108: a high affinity compound for studying binding interactions with human DNA methyltransferases.
Schirrmacher E, et al. Bioconjug Chem. 2006 Mar-Apr;17(2):261-6. PMID: 16536454.
Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines.
Stresemann C, et al. Cancer Res. 2006 Mar 1;66(5):2794-800. PMID: 16510601.
Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases.
Brueckner B, et al. Cancer Res. 2005 Jul 15;65(14):6305-11. PMID: 16024632.
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