SBIR-STTR Award

The purpose of this Phase I proposal is to automate the analysis of the Z-Tag angiogenesis assay and to screen a small collection of compounds for their potential angiogenic activity. For the latter, we propose to screen two sets of compound libraries. First, a structurally diverse compound library containing compounds with known therapeutic indices will be tested. The results from the screen will potentially suggest novel chemistry or targets for angiogenesis. The second set of compounds consists of proprietary drugs that have been advanced into clinical studies but were withdrawn due to lack of efficacy in the designated therapeutic areas. Thus, they have been shown to be safe in humans and may be efficacious in other therapeutic areas. We will screen this library to determine the angiogenic potential of the compounds. Commercialization: The Z-Tag angiogenesis assay will be commercialized to screen compounds from biotechnology and pharmaceutical companies. In addition, hits from the compound screens will be tested in mammalian tumor models or cardiovascular disease models and then advanced into clinical trials to treat cancer or cardiovascular diseases, respectively. The success of these studies will provide better anti-angiogenesis drugs to combat cancer and to provide alternative means to treat cardiovascular diseases. In addition, the integration of the zebrafish angiogenesis assay will expedite and reduce the attrition of the drug discovery process by providing a novel quantitative, in vivo tool to screen compounds in a high throughput manner

Pathological angiogenesis, the growth of new blood vessels during a disease state, contributes to over 70 diseases, including cancer. The proposed studies are a Phase II SBIR grant application focused on the preclincal development of novel anti- angiogenic small molecules discovered using transgenic zebrafish. It is expected that these compounds may be useful in treating diseases associated with pathological angiogenesis. In the Phase I studies, a zebrafish assay for discovering new anti-angiogenic compounds was automated. A chemical compound library was screened using the zebrafish assay, and two known and one novel anti-angiogenic compounds were identified. In Phase II, these compounds will be tested in in vitro angiogenesis models and in in vivo cancer models to determine if the compounds inhibit the growth of human tumors. Zebrafish and mouse models of cancer wherein human tumor cells are implanted into the animal will be used. Additional chemical compound libraries will be screened to identify more novel anti-angiogenic compounds. Pathological angiogenesis, the growth of new blood vessels, contributes to over 70 diseases, including cancer, age-related macular degeneration, diabetic blindness, and rheumatoid arthritis. Novel anti-angiogenic compounds discovered in Phase I will be tested in relevant disease models to determine whether these compounds may be therapeutically useful. Moreover, chemical compound libraries will be screened using a transgenic zebrafish assay for angiogenesis to discover additional anti-angiogenic drugs.

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