title: Effect of the leukotriene A4 hydrolase aminopeptidase augmentor 4-methoxydiphenylmethane in a pre-clinical model of pulmonary emphysema.
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.
authors: Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA.
authors: Eliseu O
authors: EO
authors: De Oliveira
authors: Kan
authors: K
authors: Wang
authors: Hye-Sik
authors: HS
authors: Kong
authors: Suhyon
authors: S
authors: Kim
authors: Matthew
authors: M
authors: Miessau
authors: Robert J
authors: RJ
authors: Snelgrove
authors: Y Michael
authors: YM
authors: Shim
authors: Mikell
authors: M
authors: Paige
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: C569939:4-methoxydiphenylmethane; D001559:Benzhydryl Compounds; D004851:Epoxide Hydrolases; D010196:Pancreatic Elastase; C043134:leukotriene A4 hydrolase