Disease relevance of Tioguanine

• Furthermore, low concentrations of TG and zidovudine were synergistic in inhibiting HIV replication in human lymphocytes (synergy volume=19 microM(2)%), without additive cytotoxicity to host lymphocytes [1].
• Treatment of human lymphocyte cultures with thioguanine produced substantial inhibition of HIV replication (IC(50)=0.035 microM, IC(95)=15.4 microM), with minimal toxicity to host lymphocytes (<10% at 15.4 microM TG, P<0.000005) [1].
• The active metabolite of mercaptopurine and thioguanine (TG), deoxythioguanosine triphosphate, was shown to be incorporated into DNA by the polymerase function of HIV-1 RT and then to abrogate RNA cleavage by HIV-1 RNaseH [1].
• Mercaptopurines have been used as anticancer agents for more than 40 years, and most acute lymphoblastic leukemias are treated with 6-mercaptopurine (6MP) or 6-thioguanine (TG) [2].

High impact information on Tioguanine

• The inhibition of Ro5-4864 binding to high affinity binding sites by TGua appeared to be due to the binding of TGua to membranes through the formation of a mixed disulfide between the 6-thiopurine and protein thiols, since the inhibition was reversed by the presence of 2-mercaptoethanol [3].
• We have shown that the molecular form responsible for the induction of the differentiation of HL-60 cells to mature forms by 6-thioguanine (TGua) is the free base, TGua, itself [Ishiguro, Schwartz, and Sartorelli (1984) J. Cell. Physiol., 121:383-390] [3].
• At 48 h these included thiouric acid, 8-hydroxy-6-mercaptopurine and 6-methylmercaptopurine (median 31, 19.5 and 8.8 microM respectively), with TIMP, 6TG, thioxanthine and thioxanthine nucleotide at median concentrations of 61, 0.79, 2.11 and 0.80 microM respectively [4].
• In regular growth medium supplemented with 10(-4) M TG (Tyr+/TG), TGr derivatives, all of which continue to express PH, occur with high frequency (approximately equal to 10(-3) [5].

References