Development of selective tight-binding inhibitors of leukotriene A4 hydrolase.

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Yuan W, Munoz B, Wong CH, Haeggstrom JZ, Wetterholm A, Samuelsson B

Development of selective tight-binding inhibitors of leukotriene A4 hydrolase.

J Med Chem. 1993 Jan 22;36(2):211-20.

PubMed ID

8423594 [ View in PubMed

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Abstract

Leukotriene A4 hydrolase is a zinc-containing enzyme which exhibits both epoxide hydrolase and aminopeptidase activities. Since the enzyme product leukotriene B4 is an inflammatory mediator, it is of interest to develop selective inhibitors of leukotriene A4 hydrolase as potential antiinflammatory agents and as mechanistic probes. A systematic study on the enzyme specificity and the inhibition of its amidase activity with more than 30 synthetic inhibitors has led to the development of an alpha-keto-beta-amino ester (26) and a thioamine (27) as tight-binding, competitive type transition-state analog inhibitors of the aminopeptidase activity, with Ki values of 46 and 18 nM, respectively. Both compounds also inhibit the epoxide hydrolase activity, with the IC50 values of 1 microM and 0.1 microM for 26 and 27, respectively.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Ubenimex	Leukotriene A-4 hydrolase	IC 50 (nM)	20000	N/A	N/A	Details