RG108, also known as N-Phthalyl-L-tryptophan, is a novel non-nucleoside inhibitor of DNA methyltransferase ((DNMT) with potential antitumor activity. It inhibits DNMT with an IC50 of 115 nM in a cell-free assay.
Physicochemical Properties
| Molecular Formula | C19H14N2O4 | |
| Molecular Weight | 334.33 | |
| Exact Mass | 334.095 | |
| CAS # | 48208-26-0 | |
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| PubChem CID | 702558 | |
| Appearance | Light yellow to light brown solid powder | |
| Density | 1.5±0.1 g/cm3 | |
| Boiling Point | 606.0±50.0 °C at 760 mmHg | |
| Melting Point | 192-194℃ | |
| Flash Point | 320.3±30.1 °C | |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C | |
| Index of Refraction | 1.741 | |
| LogP | 3.33 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 4 | |
| Heavy Atom Count | 25 | |
| Complexity | 554 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | C1=CC=C2C(=C1)C(=O)N(C2=O)[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O |
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| 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 | |
| Chemical Name | (S)-2-(1,3-dioxoisoindolin-2-yl)-3-(1H-indol-3-yl)propanoic acid. | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | RG108 effectively blocks DNA methyltransferases in vitro and does not cause covalent enzyme trapping in human cell lines. Incubating cells with low micromolar doses of RG108 resulted in considerable demethylation of genomic DNA without any observable harm. Interestingly, RG108 causes demethylation and reactivation of tumor suppressor genes, but it does not change methylation of centromeric satellite sequences [1]. In another study, the synthesis and in vitro analysis of biotinylated RG108 conjugates were investigated to determine interactions with DNA methyltransferases [2]. A recent study demonstrated that RG108 might drastically inhibit DNA methyltransferase activity in SM-derived iPS cells compared with native SMs [3]. | ||
| ln Vivo |
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| Animal Protocol |
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| References |
[1]. 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]. 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]. Efficient non-viral reprogramming of myoblasts to stemness with a single small molecule to generate cardiac progenitor cells. PLoS One. 2011;6(8):e23667. |
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| Additional Infomation | (2S)-2-(1,3-dioxo-2-isoindolyl)-3-(1H-indol-3-yl)propanoic acid is an indolyl carboxylic acid. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 1 mg/mL (2.99 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<70°C). (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9911 mL | 14.9553 mL | 29.9106 mL | |
| 5 mM | 0.5982 mL | 2.9911 mL | 5.9821 mL | |
| 10 mM | 0.2991 mL | 1.4955 mL | 2.9911 mL |