Washington, DC — Some children lack a specific enzyme known as purine nucleoside phosphorylase (PNP). These children have also been found to have profound T-cells counts despite have normal B-cell concentrations. The observation has helped establish the relationship between PNP and T-cells and led to the development of inhibitors of PNP for the treatment of T-cell proliferative disorders such as T-cell leukemias. Psoriasis, rheumatoid arthritis and Crohn's disease are also thought to benefit from a PNP inhibitor.
PNP Inhibitors and BCX-1777
BCX-1777, (1S)-1,4-dideoxy-1-C-( 4-hydroxypyrrolo[3,2-d] pyrimidin-7-yl)-1,4-imino-D-ribitol hydrochloride [1:1] is a transition state inhibitor of PNP. Inhibition of PNP results in elevated plasma 2'-deoxyguanosine (dGuo), which is converted to intracellular 2'-deoxyguanosine triphosphate (dGTP) in malignant T-cells and activated T-cells. dGTP induces cell death in these cell types.
BCX-1777 is being tested in several Phase I and Phase I/II studies. These include a Phase I/II study of intravenous BCX-1777 in refractory T-cell malignancies, a Phase I pharmacology study of BCX-1777 in refractory malignancies, a Phase I multi-center study of intravenous BCX-1777 in refractory hematologic malignancies, and a Phase I/II multi-center study of intravenous BCX-1777 in patients with refractory CTCL.
A New Study
The results of a new study entitled, "Intravenous and Oral Phamacokinetic and Pharmacodynamic Study of BCX-1777, a Novel Purine Nucleoside Phosphorylase Transition-State Inhibitor," are being presented. The work is the result of research conducted by John Michael Kilpatrick, Leigh Harman, Deborah Phillips, Jianwen Zhang, and Philip Morris, all from BioCryst Pharmaceuticals Inc., Birmingham, AL; Ronald Bukowski, from the Cleveland Clinic, Cleveland, OH; and Deborah Thomas at the M.D. Anderson Cancer Clinic, Houston, TX. The research associated with this study occurred
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Contact: Donna Krupa
djkrupa1@aol.com
703-527-7357
American Physiological Society
19-Apr-2004
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