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 2 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 The second set of compounds consists of proprietary drugs that have been advanced into clinical studies but were withdrawn due to lack of efficacy in the designated therapeutic areas.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. Project Narrative: 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. ? ? ?
| Tran, T Cameron; Sneed, Blossom; Haider, Jamil et al. (2007) Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Cancer Res 67:11386-92 |
