Vanderbilt University

Jeffery J Prusakiewicz

Lawrence J Marnett

Andrew S Felts

Chuan Ji

Kevin R Kozak

Philip J Kingsley

The presently disclosed subject matter provides derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) that are characterized by substantially reduced cyclooxygenase inhibiting activity, yet retain the ability to interact with and modulate the activities of other polypeptides such as the class of peroxisome proliferators-activated receptors (PPARs) and &#x3b3;-secretase. Also provided are methods of using the derivatives to treat pathological disorders.

Indoleacetic acid and indenacetic acid derivatives as therapeutic agents with reduced gastrointestinal toxicity

A method of detecting an activity of a COX-2 enzyme in a subject that includes obtaining a sample of the subject; detecting an amino acid eicosanoid metabolite in the sample, wherein the presence of the amino acid eicosanoid metabolite indicates the activity of the COX-2 enzyme of the subject. Preferably the amino acid eicosanoid metabolite is a PGH-Gly or HETE-Gly metabolite. The metabolite may be detected based on metabolism of a COX-2-selective substrate. Preferably, the substrate is a lipoamino acid. More preferably, the lipoamino acid is selected from NAGly, N-arachidonyl-alanine, and &#x3b4;-arachidonyl aminobutuyic acid.

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Nashville, TN, United States of America

Jeffery J Prusakiewicz