Document Detail

Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase.
MedLine Citation:
PMID:  19939518     Owner:  NLM     Status:  MEDLINE    
Prostaglandin D(2) synthesised by the hematopoietic prostaglandin D(2) synthase has a pro-inflammatory effect in allergic asthma, regulating many hallmark characteristics of the disease. Here we describe identification of hematopoietic prostaglandin D(2) synthase inhibitors including cibacron blue, bromosulfophthalein and ethacrynic acid. Expansion around the drug-like ethacrynic acid identified a novel inhibitor, nocodazole, and a fragment representing its aromatic core. Nocodazole binding was further characterised by docking calculations in combination with conformational strain analysis. The benzyl thiophene core was predicted to be buried in the active site, binding in the putative prostaglandin binding site, and a likely hydrogen bond donor site identified. X-ray crystallographic studies supported the predicted binding mode.
Jane E Weber; Aaron J Oakley; Angelika N Christ; Alan G Clark; John D Hayes; Rhonda Hall; David A Hume; Philip G Board; Mark L Smythe; Jack U Flanagan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-23
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  45     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  France    
Other Details:
Languages:  eng     Pagination:  447-54     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Masson SAS. All rights reserved.
The University of Queensland, Institute for Molecular Bioscience, Building 80, St Lucia, Queensland 4072, Australia.
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MeSH Terms
Binding Sites
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemistry,  metabolism,  pharmacology*
Glutathione Transferase / antagonists & inhibitors
Intramolecular Oxidoreductases / antagonists & inhibitors*,  chemistry,  metabolism
Lipocalins / antagonists & inhibitors*,  chemistry,  metabolism
Models, Molecular
Molecular Conformation
Nocodazole / chemistry,  metabolism,  pharmacology
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Lipocalins; 31430-18-9/Nocodazole; EC Transferase; EC 5.3.-/Intramolecular Oxidoreductases; EC R2 D-isomerase

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