Development of Improved Therapeutics for Local and Systemic Inflammation

Inflammation has been implicated in the etiology of many pain disorders and diseases including myalgia, arthralgia, tendonitis and dental and bone irritation. In the U.S., patients spend approximately USD $3 billion each year on over-the-counter drugs. NSAIDs possess anti-inflammatory, analgesic and antipyretic activities, and are therefore widely used to treat acute and chronic inflammatory disorders. Nevertheless, these agents are limited by toxicity to the GI system and increased cardiovascular risks. Therefore, this Phase 1 effort will identify novel compounds that possess both anti-inflammatory and pain mitigation activity without adverse effects using molecular topology (MT). MT is a mathematical approach used to characterize the molecular topological signature responsible for biological activity in compounds. Once the molecular signature responsible for anti-inflammatory activity has been identified, chemical databases will be screened to identify other compounds not known to possess anti-inflammatory activity. Activity of compounds will be measured using in vitro potency assays specific for COX-1, COX-2 and 5-LOX inhibition. The anticipated results from this Phase 1 effort are novel compounds in new chemical classes with favorable anti-inflammatory activity as demonstrated by an IC50 of COX-2 and 5-LOX of between 1 micromolar and 10 micromolar.