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J Enzyme Inhib Med Chem. 2002 Jun;17(3):167-74.

Database searching for thymidine and thymidylate kinase inhibitors using three-dimensional structure-based methods.

Author information

1
Celltech R&D Ltd., Great Abington, Cambridge, UK. david.manallack@denovopharma.com

Abstract

Structure-based drug design methods were used to search for novel inhibitors of herpes simplex virus type 1 (HSV-1) thymidine kinase and Mycobacterium tuberculosis thymidylate kinase. The method involved the use of crystal structure complexes to guide database searching for potential inhibitors. A number of weak inhibitors of HSV-2 were identified, one of which was found to inhibit HSV-1 TK and HSV-1 TK-deficient viral strains. Each compound tested against M. tuberculosis thymidylate kinase was found to have some activity. The best of these compounds was only 4.6-fold less potent than 3'-azido-3'-deoxythymidine-5'-monophosphate (AZTMP). This study demonstrates the utility of structure-based drug design methods in the search for novel enzyme inhibitors.

PMID:
12443042
DOI:
10.1080/14756360290032949
[Indexed for MEDLINE]

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