Robert D. Dillard

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LY315920 is a potent, selective inhibitor of recombinant human, group IIA, nonpancreatic secretory PLA2 (sPLA2). In a chromogenic isolated enzyme assay, LY315920 inhibited sPLA2 activity with an IC50 of 9 +/- 1 nM or 7.3 x 10(-6) mole fraction, which approached the stiochiometric limit of this assay. The true potency of LY315920 was defined using a(More)
Airway constriction produced by bronchoconstrictive aerosols in vivo can result in substantial postmortem pulmonary gas trapping in the guinea pig. In order to use gas trapping responses for the evaluation of potential antiasthma agents, we developed a multiple animal inhalation exposure apparatus and an accurate system for quantitating excised lung gas(More)
A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A2 (hnps-PLA2) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA2 complexed with a series of increasingly potent indole inhibitors were determined and(More)
The pharmacological significance of the carbon bridge separating the imidazoline and phenyl rings of tolazoline-like alpha adrenergic imidazolines has been investigated. Extending the carbon bridge to two carbon atoms, or deleting the carbon bridge, lowers affinity of the imidazolines for the alpha receptor and markedly decreases or abolishes efficacy(More)
Transgenic mice were created which overexpress human secretory non-pancreatic phospholipase A2 (sPLA2) pansomatically as a potential disease and drug-testing model. The mice were produced using a DNA construct in which the inducible mouse metallothionein gene promoter drives expression of a human sPLA2 minigene. High levels of sPLA2 were detected in several(More)
The primary objective of this study was to develop a functional assay that could provide rapid and reliable information on some pharmacologic characteristics of a novel inhibitor of human secretory phospholipase A2 (sPLA2). Guinea pig bronchoalveolar lavage (BAL) fluid, containing predominantly macrophages, eosinophils and epithelial cells, released(More)
Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of various types of biologically active lipids involved in inflammatory processes. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. An inhibitor of this enzyme could have therapeutic utility. A broad(More)