6-thioguanine nucleotides (6-TGNs) consist of 6-thio(deoxy)guanosine 5'-monophosphate (T(d)GMP), -diphosphate (T(d)GDP), and -triphosphate (T(d)GTP), representing the pharmacologically-active metabolites involved in drug action of thiopurines.

Guanylate kinase (GUK1) is an essential nucleoside monophosphate kinase that catalyzes the phosphorylation of guanine-monophosphate (GMP) to yield GDP, an important precursor for nucleotide synthesis (Agarwal et al. 1978). As well as this physiological role, GUK1 converts therapeutic prodrugs into their pharmacologically active metabolites. In this example, GUK1 phosphorylates 6-thioguanosine monophosphate (6TGMP) to 6-thioguanosine diphosphate (6TGDP) (Miller et al. 1977, review in Karran 2006).