SGI-1027

Description

SGI-1027 (1020149-73-8) is a potent and selective inhibitor of DNA methyl transferase inhibiting DNMT1, DNMT3A and DNMT3B with comparable potency (IC50=12.5, 8.0 and 7.5 mM respectively).1? Treatment of various cancer cell lines with SGI-1027 results in selective degradation of DNMT1 (MG-132 sensitive) with minimal effect on DNMT3A and 3B at 2.5-5 mM.1 Prolonged treatment of RKO cells resulted in reexpression of silenced tumor suppressor genes.1 Synergizes with doxorubicin at growth inhibition in neuroblastoma cell lines.2 Disrupts the MKK3-MYC complex in cells and inhibits MYC transcriptional activity in colon and breast cancer cells.3

The Uses of SGI-1027

SGI-1027 is a quinoline derivative and a potent inhibitor of DNA methyltransferase (DNMT). SGI-1027 can be used as a potential therapeutic agent for the treatment of cancer and other diseases and also as a research tool to investigate the role of DNMTs in epigenetic events.

What are the applications of Application

SGI-1027 is an inhibitor of the DNA methyltransferases

Biochem/physiol Actions

SGI-1027 is a DNA methyltransferase (DNMT) inhibitor with IC50 values of 6-13 μM for DNMT3B, DNMT3A and DNMT1. SGI-1027 directly inhibits DNMT activity by competing with the cofactor, S-adenosylmethionine (SAM) in the methylation reaction. SGI-1027 treatment of cancer cell lines induced degradation of DNMT1, but not DNMT3A or DNMT3B, and in RKO cells caused re-expression of the silenced tumor supressor genes p16, MLH1 and TIMP3.

Storage

Store at -20°C

References

Datta et al. (2009), A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation; Cancer Res., 69 4277 Penter et al. (2015) A rapid screening system evaluates novel inhibitors of DNA methylation and suggests F-box proteins as potential therapeutic targets for high-risk neuroblastoma; Target Oncol., 10 523 Yang et al. (2021), Discovery of the first chemical tools to regulate MKK3-mediated MYC activation in cancer; Bioorg. Chem., 45 116324