6-Thioguanine
Anticancer agent / downregulates DNMT1 / After incorporation into DNA, it disrupts cytosine methylation by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo.1 It reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNA methyltransferase (DNMT1).2 Incorporates into DNA and induces double strand breaks which destabilize DNA structure resulting in cytotoxicity.3 Selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance in a xenograft model.4 Anticancer and immunosuppressive activity.
Biochemicals & reagents
154-42-7
6-TG; NSC 752; NSC 76504
1) Wang and Wang (2009), 6-thioguanine perturbs cytosine methylation at the CpG dinucleotide site by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo; Biochemistry, 48 2290 2) Yuan et al. (2011), 6-thioguanine reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNMT1; Cancer Res., 71 1904 3) Bohon and de los Santos (2005), Effect of 6-thioguanine on the stability of duplex DNA; Nucleic Acid Res., 33 2880 4) Issaeva et al. (2010), 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance; Cancer Res., 70 6268
-20°C
TARGET: DNA -- PATHWAY: DNA damage; Cytotoxicity -- RESEARCH AREA: Cell death; Immunology -- DISEASE AREA: Cancer