A novel bioreductive prodrug of 6-thioguanine, 2-amino-6-[2-(4-nitrophenyl)prop-2-ylsulfanyl]-9H-purine, containing a gem-dimethyl thioether linkage, was synthesised and compared with its unsubstituted analogue. In A549 whole cell experiments hypoxia selective release of 6-thioguanine was observed with the substituted prodrug only.