SBIR-STTR Award

Development of a flow-cytometry-based method to measure the expression of cell surface molecules on endothelial cells is proposed for screening for novel regulators of inflammation. Many anti-inflammatory drugs, including corticosteroids, cyclooxygenase inhibitors and lipoxygenase inhibitors, inhibit the cytokine-dependent expression of certain endothelial cell surface molecules in culture. Our preliminary studies indicate that drugs can be distinguished based on their selective effects on particular cell surface molecules and/or under particular activation conditions. A robust assay system that can rapidly measure these effects under conditions that are more relevant to complex disease processes may be a useful tool for the rapid identification and characterization of novel anti-inflammatory drug compounds. The development of a multi-parameter flow cytometry method that allows the simultaneous measurement of multiple cell surface molecules in such a system may provide an innovative strategy for identifying and characterizing novel regulators of inflammation from synthetic or natural product libraries. PROPOSED COMMERCIAL APPLICATION: Commercial application: identifying anti-inflammatory drug compounds for pharmaceutical drug discovery

The advances in genomics and high throughput chemistry technologies have fueled the need for more rapid and biologically relevant methods to validate and prioritize lead compounds for new medicine development. Since much of the cost of drug development is due to drug failures (90% of drugs that enter clinical trials fail to become approved), providing better information earlier in the discovery process will result in significant cost savings for pharmaceutical companies and lower prices for consumers. BioSeek, Inc. is developing robust biological screening systems that provide in-depth biological information with improved pathophysiological relevance. BioMAP systems, based on Biological Multiplexed Activity Profiling, utilize primary human cell cultures in which multiple disease-relevant pathways are simultaneously active for characterization of chemical and genetic regulators of cell functions. High throughput cell profiling in a robust ELISA format using optimized proprietary sets of parameter measurements is used to rapidly identify drug mechanisms of action, off-target activities and preliminary cytotoxicity. The specific aims of this proposal include 1) scale up of an inflammation BioMAP assay systems suitable for screening compounds; 2) development of analytical tools that allow rapid identification of mechanism of action identification; 3) expansion of the database of reference compound activities; and 4) performance of pilot studies for discovery of novel therapeutic lead compounds.

Thesaurus Terms:
antiinflammatory agent, cell population study, drug screening /evaluation, enzyme linked immunosorbent assay, high throughput technology, immunoregulation, inflammation, method development chemical registry /resource, chemokine, cytokine, flow cytometry, immunomodulator