Preliminary report on 8-amino-9-(2-thienylmethyl)guanine (PD 119,229), a novel and potent purine nucleoside phosphorylase inhibitor.

PD 119,229 [8-amino-9-(2-thienylmethyl)guanine] is a novel and potent inhibitor of human erythrocyte purine nucleoside phosphorylase (PNP) with a Ki of 0.067 microM. In a cell line assay using human MOLT-4 (T cell) and MGL-8 (B cell) lymphoblasts, PD 119,229 alone had no effect on the growth of either cell line at the highest concentration tested (100 microM). However, in the presence of a nontoxic concentration of 2'-deoxyguanosine (10 microM), the IC50 values of PD 119,229 for MOLT-4 and MGI-8 40-fold either cell line at the highest concentration tested (100 microM). However, in the presence of a nontoxic concentration of 2'-deoxyguanosine (10 microM), the IC50 values of PD 119,229 for MOLT-4 and MGI-8 were 0.9 and greater than 100 microM, respectively. The inhibition of growth of MOLT-4 was accompanied by a 40-fold increase in dGTP and a two-fold reduction in GTP, while no alteration in nucleotide profile was noted in MGL-8. Both the inhibition of growth of MOLT-4 and the accumulation of dGTP were substantially prevented by coaddition of 2'-deoxycytidine.