Chemical Name: 2-Amino-6-mercaptopurine
Biological ActivityAnticancer and immunosuppressive agent often used to treat immune disorders and leukemia. Displays cytotoxic and antineoplastic properties; disrupts cytosine methylation by DNA methyltransferases after incorporation into DNA. Selectively kills BRCA2-defective tumors in a xenograft model. Also facilitates proteasome-mediated degradation of DNA (cytosine-5)-methyltransferase 1 (DNMT1). Also inhibits SARS-CoV papain-like protease (PLpro; IC50 = 5 μM for PLpro deubiquitination activity).
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6-thioguanine reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNMT1.
Yuan et al.
Cancer Res., 2011;71:1904
6-Thioguanine perturbs cytosine methylation at CgP dinucleotide site by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo.
Wang and Wang
6-Thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.
Issaeva et al.
Cancer Res., 2010;70:6268
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6-Thioguanine was incorporated into the RNA of all subcellular fractions, but to different extents and it also appears to be incorporated into a non-nucleotide fraction in the cell walk.