48208-26-0 Usage
Description
RG108, also known as [2-(1,3-dioxoisoindolin-2-yl)-3-(1H-indol-3-yl) propanoic acid, is a non-nucleoside DNA methyltransferase inhibitor with an IC50 of 115 nM in vitro. It is effective in inhibiting DNA methylation in human tumor cell lines without causing toxicity. RG108 works by blocking the enzyme active site, leading to demethylation and reactivation of epigenetically silenced tumor suppressor genes. RG108 has potential applications in various fields, including cancer treatment and cell reprogramming.
Uses
Used in Cancer Treatment:
RG108 is used as a DNA methyltransferase inhibitor for its ability to reduce the methylation of genomic DNA in cells, leading to the reactivation of epigenetically silenced tumor suppressor genes. This action contributes to the inhibition of tumor growth and progression.
Used in Cell Reprogramming and Increasing Cell Plasticity:
RG108 is used in reprogramming and increasing the plasticity of primary multipotent mesenchymal stromal cells (MMSC), enhancing their potential for therapeutic applications.
Used in Human Retinal Pigment Epithelial ARPE-19 Cells:
RG108 is used as an inhibitor of DNA methyltransferase (DNMTi) in human retinal pigment epithelial ARPE-19 cells, potentially contributing to the understanding and treatment of related conditions.
Used in C33A2 Cells for Papillomavirus Late Gene Expression (HPV16):
RG108 is used as a DNA methyltransferase inhibitor in C33A2 cells to test its effect on papillomavirus late gene expression, which could have implications for the development of treatments for HPV16-related diseases.
Biological Activity
Non-nucleoside DNA methyltransferase inhibitor that blocks the enzyme active site. Inhibits DNA methylation in human cancer cell lines in vitro without detectable toxicity. Demethylates and reactivates epigenetically silenced tumor suppressor genes.
Biochem/physiol Actions
RG108 is a DNA methyltransferase (DMNT) inhibitor. It reactivates tumor suppressor gene expression (p16, SFRP1, secreted frizzled related protein-1, and TIMP-3) in tumor cells by DNA demethylation. RG108 also inhibits human tumor cell line (HCT116, NALM-6) proliferation and increased doubling time in culture.
References
1) Brueckner et al. (2005), Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferase; Cancer Res., 65 6305
2) Stresemann et al. (2006), Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines; Cancer Res., 66 2794
3) Szablowska-Gadomska et al. (2012), Treatment with small molecules is an important milestone towards the induction of pluripotency in neural stem cells derived from human cord blood; Acta Neurobiol. Exp., 72 337
Check Digit Verification of cas no
The CAS Registry Mumber 48208-26-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 4,8,2,0 and 8 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 48208-26:
(7*4)+(6*8)+(5*2)+(4*0)+(3*8)+(2*2)+(1*6)=120
120 % 10 = 0
So 48208-26-0 is a valid CAS Registry Number.
InChI:InChI=1/C19H16N2O4/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/h3-8,10,16,20H,1-2,9H2,(H,24,25)/t16-/m0/s1
48208-26-0Relevant articles and documents
Convergent Synthesis of Calcium-Dependent Antibiotic CDA3a and Analogues with Improved Antibacterial Activity via Late-Stage Serine Ligation
Blasco, Pilar,Chen, Delin,Chen, Sheng,Li, Xuechen,Po, Kathy Hiu Laam
supporting information, (2020/06/29)
A convergent synthesis via the late-stage serine ligation of naturally occurring calcium-dependent antibiotic CDA3a and its analogues has been developed, which allowed us to readily synthesize the analogues with the variation on the lipid tail. Some analogues were found to show 100-500-fold higher antimicrobial activity than the natural compound CDA3a against drug resistant bacteria. This study will enhance our understanding of CDA3a and provide valuable antibacterial lead candidates for further development.
Synthesis and evaluation of analogues of N-phthaloyl-l-tryptophan (RG108) as inhibitors of DNA methyltransferase 1
Asgatay, Saa?dia,Champion, Christine,Marloie, Ga?l,Drujon, Thierry,Senamaud-Beaufort, Catherine,Ceccaldi, Alexandre,Erdmann, Alexandre,Rajavelu, Arumugam,Schambel, Philippe,Jeltsch, Albert,Lequin, Olivier,Karoyan, Philippe,Arimondo, Paola B.,Guianvarc'H, Dominique
, p. 421 - 434 (2014/02/14)
DNA methyltransferases (DNMT) are promising drug targets in cancer provided that new, more specific, and chemically stable inhibitors are discovered. Among the non-nucleoside DNMT inhibitors, N-phthaloyl-l-tryptophan 1 (RG108) was first identified as inhibitor of DNMT1. Here, 1 analogues were synthesized to understand its interaction with DNMT. The indole, carboxylate, and phthalimide moieties were modified. Homologated and conformationally constrained analogues were prepared. The latter were synthesized from prolinohomotryptophan derivatives through a methodology based amino-zinc-ene-enolate cyclization. All compounds were tested for their ability to inhibit DNMT1 in vitro. Among them, constrained compounds 16-18 and NPys derivatives 10-11 were found to be at least 10-fold more potent than the reference compound. The cytotoxicity on the tumor DU145 cell line of the most potent inhibitors was correlated to their inhibitory potency. Finally, docking studies were conducted in order to understand their binding mode. This study provides insights for the design of the next-generation of DNMT inhibitors.
Stereoselective synthesis of brevianamide e
Zhao, Liang,May, Jonathan P.,Huang, Jack,Perrin, David M.
supporting information; experimental part, p. 90 - 93 (2012/02/15)
The hydroxypyrroloindolenine (Hpi) motif forms the fundamental core of the pentacyclic natural product, brevianamide E, the concise stereoselective synthesis of which, via oxidative cyclization, is described.
