Document Detail


Inhibitors of the enzyme purine nucleoside phosphorylase as potential therapy for psoriasis.
MedLine Citation:
PMID:  10828318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Purine nucleoside phosphorylase (PNP) is one of the enzymes comprising the purine salvage pathway , and is responsible for the catalysis of the reversible phosphorolytic cleavage of purine ribonucleosides and 2'-deoxyribonucleosides. The pivotal role of PNP in T-cell proliferation has been demonstrated in patients with inherited PNP deficiency, where T-cell levels may be 1-3% of normal. This observation helped establish the critical role of PNP in T-cells and provided a rationale for developing inhibitors of PNP. Inhibitors of PNP may be useful for treating a variety of T-cell related autoimmune diseases including psoriasis, rheumatoid arthritis and Crohn s disease and T-cell cancers. In this manuscript, the x-ray crystal structure of the PNP enzyme is described. Results of a structure-based drug design program aimed at designing small-molecule inhibitors of PNP are also described. Of the many classes of compounds synthesized, studied and reviewed, only one, the 3-pyridinylmethyl-9-deazaguanine (BCX-34, 39) analog has been used in clinical trials. Both topical and oral formulations of BCX-34 were studied in psoriatic patients and the results of these clinical trials are described.
Authors:
P E Morris; G A Omura
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  6     ISSN:  1381-6128     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-07-31     Completed Date:  2000-07-31     Revised Date:  2006-02-27    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  943-59     Citation Subset:  IM    
Affiliation:
BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA. pmorris@biocryst.com
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MeSH Terms
Descriptor/Qualifier:
Drug Design
Enzyme Inhibitors / pharmacology,  therapeutic use*
Guanine / analogs & derivatives*,  pharmacology,  therapeutic use
Humans
Models, Molecular
Psoriasis / drug therapy*,  enzymology
Purine-Nucleoside Phosphorylase / antagonists & inhibitors*,  physiology
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 133432-71-0/peldesine; 73-40-5/Guanine; EC 2.4.2.1/Purine-Nucleoside Phosphorylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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