DNA Methyltransferase Inhibitor II, SGI-1027

A cell-permeable quinoline compound that is shown to inhibit human DNMT1 (IC₅₀ = 6 and 12.5 µM, respectively, with Hemimethylated DNA or Poly(dI-dC) as the substrate), murine DNMT3a & 3b (IC₅₀ = 8 and 7.5 µM, respectively, with Poly(dI-dC) as the substrate), as well as CpG DNA methylase M.SssI (IC₅₀ = 13.5 and 16 µM, respectively, with Poly(dI-dC) as the substrate and 75 or 150 nM AdoMet) of mycoplasma Spiroplasma sp. strain MQ1, presumably by competing with AdoMet (S-adenosyl-L-methionine , SAM) for the enzyme′s cofactor binding site. Shown to be 2-, 3-, and 5-fold more effective than Decitabine (Cat. No. 189825), respectively, in reactivating p16 mRNA (2.5 µM for 7 days), MLH1 mRNA (2.5 µM for 7 days), and p16 protein expression (1.0 or 2.5 µM for 12 days) in human colon carcinoma RKO cultures by reducing CpG island hypermethylation found in the promoter regions of TSGs (tumor suppressor genes) without inducing genome-wide hypomethylation or caspase-3 activation.

A cell-permeable quinoline compound that is shown to inhibit human DNMT1 (IC₅₀ = 6 and 12.5 µM, respectively, with Hemimethylated DNA or Poly(dI-dC) as the substrate), murine DNMT3a & 3b (IC₅₀ = 8 and 7.5 µM, respectively, with Poly(dI-dC) as the substrate), as well as CpG DNA methylase M.SssI (IC₅₀ = 13.5 and 16 µM, respectively, with Poly(dI-dC) as the substrate and 75 or 150 nM AdoMet) of mycoplasma Spiroplasma sp. strain MQ1, presumably by competing with AdoMet (S-adenosyl-L-methionine , SAM) for the enzyme′s cofactor binding site. Shown to be 2-, 3-, and 5-fold more effective than Decitabine (Cat. No. 189825), respectively, in reactivating p16 mRNA (2.5 µM for 7 days), MLH1 mRNA (2.5 µM for 7 days), and p16 protein expression (1.0 or 2.5 µM for 12 days) in human colon carcinoma RKO cultures by reducing CpG island hypermethylation found in the promoter regions of TSGs (tumor suppressor genes) without inducing genome-wide hypomethylation or caspase-3 activation.

Packaged under inert gas

Toxicity: Standard Handling (A)

Datta, J., et al. 2009. Cancer Res.69, 4277.

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