This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Angiogenesis is a complex biological process that controls the growth of new blood vessels in the body. Normally, angiogenesis is down-regulated in adults, with the exception of wound healing and the menstrual cycle. Aberrant angiogenesis, however, has been implicated in a variety of diseases, including cancer, arthritis, and retinopathy. The promise of anti-angiogenic agents in cancer therapy came to fruition in early 2004 with FDA approval of both Erbitux (Imclone) and Avastin (Genentech) for the treatment of metastatic colon cancer. These molecules are both monoclonal antibodies that bind to growth factors that enable cancer cells to grow towards and around tumors. Without a blood supply, tumors are unable to grow beyond 2 mm in diameter. Thus anti-angiogenesis cancer therapy is already prolonging and saving thousands of peoples lives. It would be particularly advantageous to develop small molecules that can inhibit angiogenesis with the same or greater efficacy as the proteins described above. Small molecules offer distinct advantages in that they can usually be administered orally, and they are far less costly than protein drugs. This proposal outlines an important scientific problem involving drug discovery in the field of cancer research. It targets the synthesis of a natural product, Fusarochromanone, and its novel amide analogs with potent anti-angiogenic activity. Fusarochromanone is also known to exhibit activity against a variety of cancer cell lines as well. Thus, this research could ultimately enhance our knowledge of angiogenesis and the growth factors that control both the growth of blood vessel cells and cancer cells.
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