Blockade of nucleoside degradation in monkey whole blood in vitro by CI-1000, a purine nucleoside phosphorylase (PNP) inhibitor.

  title={Blockade of nucleoside degradation in monkey whole blood in vitro by CI-1000, a purine nucleoside phosphorylase (PNP) inhibitor.},
  author={R. Gilbertsen and M. Dong},
  journal={Advances in experimental medicine and biology},
Purine nucleosides HxR or GdR (2.5 micrograms/mL blood) were added to EDTA-treated cynomolgus monkey whole blood in vitro, alone or with the PNP inhibitor CI-1000 (1 microgram/mL), mixed, and the concentration of nucleosides remaining in plasma followed as a function of time. The half-lives of GdR and HxR in control blood were 1.2 and < 1 min, respectively, and were extended to 17.8 and 39.8 min, respectively, by coaddition of CI-1000. In contrast, a structural analog of CI-1000, CI-972, when… Expand
4 Citations
Intravenous and oral pharmacokinetic study of BCX-1777, a novel purine nucleoside phosphorylase transition-state inhibitor. In vivo effects on blood 2'-deoxyguanosine in primates.
The data indicate that oral and IV administration of BCX-1777 induce a rapid rise in 2'-deoxyguanosine and that oral dosing at 8.8 and 17.6 mg/kg are at least equivalent to 4.4mg/kg IV in effecting the accumulation of 2'- deoxyguosine. Expand
Purine nucleoside phosphorylases: properties, functions, and clinical aspects.
Detailed accounts are presented of design of potent inhibitors, largely nucleosides and acyclonucleosides, their phosphates and phosphonates, particularly of the human erythrocyte enzyme intended for induction of the immunodeficient state for clinical applications, such as prevention of host-versus-graft response in organ transplantations. Expand
Plasma Uridine as well as Uric Acid is Elevated Following Fructose Loading
The hyperuricaemia following fructose loading was first demonstrated by Perheen-tupa and Raivio in 1967 (1). Subsequent studies (reviewed in 2) established that this elevation of plasma and urineExpand
The transition to magic bullets - transition state analogue drug design.
A brief history of transition state analogue design, the fundamentals behind the development of this process, and the success of enzyme inhibitors produced using this drug design methodology are looked at. Expand


Selective in vitro inhibition of human MOLT-4 T lymphoblasts by the novel purine nucleoside phosphorylase inhibitor, CI-972.
Inhibition of MOLT-4 growth was associated with an increase in dGTP that was dependent on CI-972 concentration and inhibited by 2'-deoxycytidine, and growth could not be restored by hypoxanthine or adenine. Expand
Comparative in vitro and in vivo activities of two 9-deazaguanine analog inhibitors of purine nucleoside phosphorylase, CI-972 and PD 141955.
An in-parallel comparison is presented of the in vitro and in vivo properties of two 9-deazaguanine analog inhibitors of purine nucleoside phosphorylase (PNP) and PD 141955, with PD considerably more potent and active in all systems studied. Expand
Evidence for a Pathway Independent from 2′‐Deoxyguanosine and Reversible by IL‐2 by which Purine Nucleoside Phosphorylase Inhibitors Block T‐Cell Proliferation
The authors' observations suggest the potential use of PNP inhibitors in the therapy of cutaneous T‐cell lymphomas and provide evidence for a pathway independent from deoxyguanosine by which P NP inhibitors might function in T cells. Expand
Effects of 8‐Aminoguanosine, an Inhibitor of Purine Nucleoside Phosphorylase, on Plasma Nucleosides in Wistar Rats
Immunodeficient patients lacking the purine degradative enzyme purine nucleoside phosphorylase (PNP, EC have elevated PNP substrates (primarily inosine and guanosine) both in plasma andExpand
Inhibitors of human purine nucleoside phosphorylase. Synthesis of pyrrolo[3,2-d]pyrimidines, a new class of purine nucleoside phosphorylase inhibitors as potentially T-cell selective immunosuppressive agents. Description of 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d] pyrimidin-4-on
One of the compounds, 2,6-diamino-3,5- dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidine-4-one (11c; CI-972), was found to be moderately potent, competitive, and reversible inhibitor of PNP and was evaluated further. Expand
Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.
  • S. Ealick, Y. Babu, +4 authors J. Secrist
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1991
Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported. Expand