WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406615
CAS#: 48208-26-0
Description: RG108 is a non-nucleoside DNA methyltransferase inhibitor (DNMT inhibitor). RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA reexpression was only attained for GSTP1 and APC. RG108 is an effective tumor growth suppressor in most PCa cell lines tested.
MedKoo Cat#: 406615
Name: RG108
CAS#: 48208-26-0
Chemical Formula: C19H14N2O4
Exact Mass: 334.0954
Molecular Weight: 334.33
Elemental Analysis: C, 68.26; H, 4.22; N, 8.38; O, 19.14
Synonym: RG108; RG-108; RG 108; N-Phthalyl-L-tryptophan.
IUPAC/Chemical 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)[C@H](CC1=CNC2=CC=CC=C12)N3C(C4=CC=CC=C4C3=O)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | RG108 is a non-nucleoside DNA methyltransferases (DNMTs) inhibitor (IC50=115 nM) that blocks the DNMTs active site. RG108 causes demethylation and reactivation of tumor suppressor genes, but it does not affect the methylation of centromeric satellite sequences. |
| In vitro activity: | This study proposes that RG108 could be used for epigenetic modulation, because it promotes epigenetic activation of NANOG and OCT4 without affecting the viability of human bone marrow-derived mesenchymal stem cells. RG108 is a stronger modulator of epigenetic machinery enzymes than DMSO. Reference: PLoS One. 2018 Dec 3;13(12):e0207873. https://pubmed.ncbi.nlm.nih.gov/30507955/ |
| In vivo activity: | Inhibition of DNA methyltransferase activity via RG108 significantly attenuated auditory brainstem response threshold elevation, hair cell damage, and the loss of auditory synapses. RG108 protected against noise-induced hearing loss, protected against noise-induced hair cell loss and auditory neural damage, and attenuated oxidative stress-induced DNA damage and subsequent apoptosis-mediated cell loss in the cochlea after noise exposure. Reference: Cell Biol Toxicol. 2021 Oct;37(5):751-771. https://pubmed.ncbi.nlm.nih.gov/33723744/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 299.11 |
The following data is based on the product molecular weight 334.33 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Assis RIF, Wiench M, Silvério KG, da Silva RA, Feltran GDS, Sallum EA, Casati MZ, Nociti FH Jr, Andia DC. RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation. PLoS One. 2018 Dec 3;13(12):e0207873. doi: 10.1371/journal.pone.0207873. PMID: 30507955; PMCID: PMC6277091. 2. Yang L, Hou J, Cui XH, Suo LN, Lv YW. RG108 induces the apoptosis of endometrial cancer Ishikawa cell lines by inhibiting the expression of DNMT3B and demethylation of HMLH1. Eur Rev Med Pharmacol Sci. 2017 Nov;21(22):5056-5064. doi: 10.26355/eurrev_201711_13818. PMID: 29228451. 3. Zheng Z, Zeng S, Liu C, Li W, Zhao L, Cai C, Nie G, He Y. The DNA methylation inhibitor RG108 protects against noise-induced hearing loss. Cell Biol Toxicol. 2021 Oct;37(5):751-771. doi: 10.1007/s10565-021-09596-y. Epub 2021 Mar 15. PMID: 33723744; PMCID: PMC8490244. 4. Zhai Y, Zhang Z, Yu H, Su L, Yao G, Ma X, Li Q, An X, Zhang S, Li Z. Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs. Cell Physiol Biochem. 2018;50(4):1376-1397. doi: 10.1159/000494598. Epub 2018 Oct 24. PMID: 30355946. |
| In vitro protocol: | 1. Assis RIF, Wiench M, Silvério KG, da Silva RA, Feltran GDS, Sallum EA, Casati MZ, Nociti FH Jr, Andia DC. RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation. PLoS One. 2018 Dec 3;13(12):e0207873. doi: 10.1371/journal.pone.0207873. PMID: 30507955; PMCID: PMC6277091. 2. Yang L, Hou J, Cui XH, Suo LN, Lv YW. RG108 induces the apoptosis of endometrial cancer Ishikawa cell lines by inhibiting the expression of DNMT3B and demethylation of HMLH1. Eur Rev Med Pharmacol Sci. 2017 Nov;21(22):5056-5064. doi: 10.26355/eurrev_201711_13818. PMID: 29228451. |
| In vivo protocol: | 1. Zheng Z, Zeng S, Liu C, Li W, Zhao L, Cai C, Nie G, He Y. The DNA methylation inhibitor RG108 protects against noise-induced hearing loss. Cell Biol Toxicol. 2021 Oct;37(5):751-771. doi: 10.1007/s10565-021-09596-y. Epub 2021 Mar 15. PMID: 33723744; PMCID: PMC8490244. 2. Zhai Y, Zhang Z, Yu H, Su L, Yao G, Ma X, Li Q, An X, Zhang S, Li Z. Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs. Cell Physiol Biochem. 2018;50(4):1376-1397. doi: 10.1159/000494598. Epub 2018 Oct 24. PMID: 30355946. |
1: Asgatay S, Champion C, Marloie G, Drujon T, Senamaud-Beaufort C, Ceccaldi A, Erdmann A, Rajavelu A, Schambel P, Jeltsch A, Lequin O, Karoyan P, Arimondo PB, Guianvarc'h D. Synthesis and evaluation of analogues of N-phthaloyl-l-tryptophan
(RG108) as inhibitors of DNA methyltransferase 1. J Med Chem. 2014 Jan 23;57(2):421-34. doi: 10.1021/jm401419p. Epub 2014 Jan 9. PubMed PMID: 24328113.
2: Graça I, Sousa EJ, Baptista T, Almeida M, Ramalho-Carvalho J, Palmeira C, Henrique R, Jerónimo C. Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cells. Curr Pharm Des. 2014;20(11):1803-11. PubMed PMID: 23888969.
3: Savickiene J, Treigyte G, Jazdauskaite A, Borutinskaite VV, Navakauskiene R. DNA methyltransferase inhibitor RG108 and histone deacetylase inhibitors cooperate to enhance NB4 cell differentiation and E-cadherin re-expression by chromatin remodelling. Cell Biol Int. 2012 Nov 1;36(11):1067-78. doi: 10.1042/CBI20110649. PubMed PMID: 22845560.
4: Savickiene J, Treigyte G, Borutinskaite VV, Navakauskiene R. Antileukemic activity of combined epigenetic agents, DNMT inhibitors zebularine and RG108 with HDAC inhibitors, against promyelocytic leukemia HL-60 cells. Cell Mol Biol Lett. 2012 Dec;17(4):501-25. Epub 2012 Jul 20. PubMed PMID: 22820861.
5: Braun J, Boittiaux I, Tilborg A, Lambert D, Wouters J. The dicyclo-hexyl-amine salt of RG108 (N-phthalyl-l-tryptophan), a potential epigenetic modulator. Acta Crystallogr Sect E Struct Rep Online. 2010 Nov 13;66(Pt 12):o3175-6. doi: 10.1107/S160053681004626X. PubMed PMID: 21589471; PubMed Central PMCID: PMC3011641.
6: Schirrmacher E, Beck C, Brueckner B, Schmitges F, Siedlecki P, Bartenstein P, Lyko F, Schirrmacher R. 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. PubMed PMID: 16536454.
