Description:
IC50 Value: 0.6 mM (ID50, 24 h exposure to HL-60 cell) [1]
6-TG belongs to the thiopurine family of drugs that also include mercaptopurineand azathioprine, which are examples of antimetabolites. It is a purine analogue of the nucleobase guanine.
in vitro:  6-TG was toxic to HL-60 cells (ID50 = 0.6 microM; 24-h exposure) while IFN-alpha (up to 1000 IU/ml) had minimal cytotoxic activity [1]. Paradoxically, inhibition of c-myc expression in the wild type HL-60 (HL-60/wt) cell, which is only weakly induced to differentiate by TG, was 5-fold more sensitive to the thiopurine (IC50 = 35 microM) [2].
in vivo: SOS did not occur in hypoxanthine-phosphoribosyl transferase-deficient C57Bl/6 mice, demonstrating that 6TG-SOS requires thioguanine nucleotides [3]. A higher fraction of the dose was recovered in urine as the parent thiopurine and the metabolites thiopurine riboside, thioxanthine, and thiouric acid after 6-TG treatment than after trans-AVTG treatment; cis-AVTP recovery was slightly less than that of 6-TG [4].
Clinical trial: 6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients. Phase 2