1020149-73-8

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Uses

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.

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.

Synthesis

20719-43-1

133041-90-4

1020149-73-8

GENERAL STEPS: 4-(quinolin-4-ylamino)benzoic acid (45 mg, 0.17 mmol) and N4-(4-aminophenyl)-6-methylpyrimidine-2,4-diamine (37 mg, 0.17 mmol) were dissolved in DMF (1.7 mL). Subsequently, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.06 g, 0.34 mmol) and 1-hydroxybenzotriazole hydrate (0.03 g, 0.17 mmol) were added sequentially. The reaction mixture was stirred at 65oC for 24 hours. After completion of the reaction, the solvent was removed by vacuum concentration and the residue was purified by column chromatography (silica gel, eluent ratio 85:13:2 dichloromethane/methanol/triethylamine) to afford N-[4-[(2-amino-6-methyl-4-pyrimidinyl)amino]phenyl]-4-(4-quinolinylamino)benzamide (0.05 g, 59% yield) as an amorphous yellow solid.

target

DNMT1

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

Questions And Answer

• Description

  SGI-1027 is a DNMT inhibitor with IC50 of 6, 8, 7.5 μM for DNMT1, DNMT3A, and DNMT3B in cell-free assays, respectively. ;

• Features

  Potential for use in epigenetic cancer therapy.;

• In vitro

  SGI-1027 inhibits DNA methylation by directly inhibiting DNMTs, and results in selective degradation of DNMT1 in a wide variety of human cancer cell lines. SGI-1027 exhibits minimal or no cytotoxic effect in rat hepatoma H4IIE cells.  SGI-1027 (0-100 μM) exhibits a moderate pro-apoptotic effect on U937 human leukemia cell line with no relevant changes on the cell cycle. ;

Spectrum Detail

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