Changes in Monkey Plasma Purines Induced by Repeated Doses of CI-1000, a Novel Inhibitor of Purine Nucleoside Phosphorylase

CI-1000, a 9-deazaguanine analog, is an orally active and reversible inhibitor of purine nucleoside Phosphorylase (PNP). In vitro, CI-1000 inhibits human T-lymphoblast replication and the mixed lymphocyte response, as well as facilitating the intracellular accumulation of deoxyguanosine triphosphate (Gilbertsen et al., 1992; Dong and Gilbertsen, 1993; Wilburn et al. 1993). These changes are consistent with inhibition of PNP (Osborne and Scott, 1983; Fairbanks et al., 1990; Gilbertsen and Sircar, 1990) and the drug is approximately 10-fold more potent than a structurally related compound (Gilbertsen et al., 1991a, 1991b, and 1992).