Effect of the Leukotriene A4 Hydrolase Aminopeptidase Augmentor 4-methoxydiphenylmethane in a Pre-clinical Model of Pulmonary Emphysema

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2011 Oct 11

PMID 21983441

Citations 6

Authors

Eliseu O De Oliveira

Kan Wang

Hye-Sik Kong

Suhyon Kim

Matthew Miessau

Robert J Snelgrove

Y Michael Shim

Mikell Paige

Affiliations

Soon will be listed here.

Abstract

The leukotriene A(4) hydrolase enzyme is a dual functioning enzyme with the following two catalytic activities: an epoxide hydrolase function that transforms the lipid metabolite leukotriene A(4) to leukotriene B(4) and an aminopeptidase function that hydrolyzes short peptides. To date, all drug discovery efforts have focused on the epoxide hydrolase activity of the enzyme, because of extensive biological characterization of the pro-inflammatory properties of its metabolite, leukotriene B(4). Herein, we have designed a small molecule, 4-methoxydiphenylmethane, as a pharmacological agent that is bioavailable and augments the aminopeptidase activity of the leukotriene A(4) hydrolase enzyme. Pre-clinical evaluation of our drug showed protection against intranasal elastase-induced pulmonary emphysema in murine models.

Citing Articles

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