Reference #: 00124
Invention Description:
The subject invention describes the use of Fusarochromanone (FC101), a fungal metabolite known to cause avian tibial dyschondroplasia. FC101 is an inhibitor of angiogenesis, lymphocytic development, and importantly the proliferation of many human cancer cell lines. FC101 has highly selective action, inhibiting growth of many melanoma cell lines with IC50 values in the 0.5 nM range, as well as various lung cancer and colon cancer cells in the 10-50 nM range. FC101 has low toxicity toward nonproliferating cells, but does inhibit proliferation of normal vascular endothelial cells involved in angiogenesis, with an IC50 value of ~50 nM. It also has been shown to inhibit in vivo lymphocyte formation. FC101 has little effect on the proliferation of chondrocytes from several species (IC50 ~3,000 nM). The drug was found to inhibit well over half of the 60 human cancer cell lines used in the screening assay of the National Cancer Institute Drug Development Program. Continuing research reveals that FC101 has the potential to develop into an effective anti-cancer drug.
Background:
Angiogenesis, the formation of new capillary blood vessels, is crucial to tumor development and for metastasis. While perivascular tumors may exist as thin, asymptomatic lesions restricted by the limits of oxygen and nutrient diffusion, vascularized tumors can expand locally and by metastasis. There is abundant evidence that tumors can induce angiogenesis through elaboration of various soluble factors. Hence, it is desirable to develop angiogenesis inhibitors to curb tumor growth and metastasis. Indeed, several angiogenesis inhibitors have been found that promote tumor shrinkage and inhibit spreading of cancer cells.
Potential Applications:
The immediate application of FC101 is to provide a lead-compound for the development of chemotherapeutic agents for the treatment of a variety of angiogenesis based diseases.
These angiogenesis diseases include the following:
- cancer
- psoriasis
- diabetic retinopathy
- and various other vascularization-related eye disorders
Advantages and Benefits:
FC101 is toxic to the proliferation of endothelial cells
FC101 is nontoxic to the growth of other tissue cell types
FC101 is likely safer for administration as an anti-tumor drug than most agents currently available
FC101 offers the potential of being used in combination with existing drugs to provide a more aggressive treatment regimen in tumor chemotherapy
Development / Demonstration / Validation:
Extensive in vitro testing has been carried out to determine the effectiveness of FC 101. FC 101's results have been impressive in slowing the growth of cancer cells while possessing very low toxicity.