Disease relevance of NSC 12160

• Regression of experimental brain tumors with 6-thioxanthine and Escherichia coli gpt gene therapy [1].
• In a nude mouse model of subcutaneous tumors, co-grafts of C6 glioma and gpt-retrovirus producer cells displayed retarded growth upon exposure to 6-thioxanthine (6-TX) [1].
• In mice, systemic 6TX therapy induced durable regressions in 19/20 gpt-positive K3T3 sarcomas without affecting gpt-negative tumors [2].

High impact information on NSC 12160

• Insertional mutagenesis has been carried out on this parental line, followed by bradyzoite induction in vitro and selection in 6-thioxanthine to identify misregulation mutants [3].
• The ES-E14TG2a murine embryonic stem cell line was rendered sensitive to quantitative ablation at prodrug concentrations well tolerated by untransduced cells (50 microM 6TX, 1 microg/ml GCV) [4].
• Escherichia coli gpt gene sensitizes rat glioma cells to killing by 6-thioxanthine or 6-thioguanine [5].
• 6-Thioxanthine was a substrate of the parasite's hypoxanthine-guanine phosphoribosyltransferase [6].
• 6-Thioxanthine caused 50% inhibition of the growth of Toxoplasma gondii in human fibroblasts at a concentration of 5 micrograms/ml [7].

Chemical compound and disease context of NSC 12160

• Unlike other genes tested to date in brain tumor models, the Escherichia coli gpt gene is unique in that it not only sensitizes cells to the prodrug 6-thioxanthine (6TX) but also encodes resistance to a different regimen (mycophenolic acid, xanthine, and hypoxanthine), thus providing a means to select for gpt-positive cells [5].

Biological context of NSC 12160

• Xanthine oxidase-catalyzed hydroxylation reactions of the anticancer drug 6-mercaptopurine (6-MP) and its analog 2-mercaptopurine (2-MP) as well as 6-thioxanthine (6-TX) and 2-thioxanthine (2-TX) have been studied using UV-spectroscopy, high pressure liquid chromatography, photodiode array, and liquid chromatography-based mass spectral analysis [8].

References