Novel Methods for Inhibiting Angiogenesis

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Developed by:

  • Margie L. Clapper, PhD

  • Background:

    Angiogenesis, the creation of new blood vessels, is significant for both normal and aberrant body processes. For example, it is involved in normal tissue development, as well as the establishment and maintenance of tumors. The ability of certain vegetables to delay or inhibit cancer has been well-documented, and sulfur-containing substances known as dithiolthiones, found in the Cruciferae vegetable family, emphasize this features. These compounds are implicated in the activation of detoxification enzymes, such as those that eliminate carcinogens. Oltipraz [(5-2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] is a manufactured dithiolthione that has demonstrated high efficiency in an extremely aggressive mouse angiosarcoma xenograft model.


    Chemotherapy: Based on its potent anti-angiogenic activity, Oltipraz may be utilized to augment the regression of existing cancer cells, especially in angiosarcoma.
    Drug Discovery: In addition, due to its lack of organ specificity, Oltipraz may prove vital for the inhibition of drug resistant malignancies and may represent a model compound after which other dithiolthione derivatives may be manufactured, increasing the present arsenal of medications for cancer.


    Trials conducted in colon, breast, liver, and lung cancer patients demonstrated minimal toxicity of Olitpraz in humans, and its effects are equivalent to anti-angiogenic standards. Also, due to the absence of specific target organ and substrate specificity, the emergence of tumor cell resistance is unlikely. Importantly, in the angiosarcoma xenograft model, Oltipraz has exhibited both chemopreventive and chemotherapeutic effects by restricting new blood vessel formation and interrupting the establishment of tumor growth. The compound has also arrested the emergence and advancement of a variety of rodent tumor types, such as breast, colon, lung, skin, pancreas, and liver. Therefore, the anti-angiogenic activity of Oltipraz dictates an innovative application of the dithiolthione class of agents for cancer treatment. It should be noted that reversible numbness and pain in the extremities has been associated with Oltipraz use in some settings.


    We are seeking an exclusive licensee, preferably one who would sponsor a Phase I clinical trial of Oltipraz in angiosarcoma at Fox Chase Cancer Center.

    Patent Status:

     U.S. Patent 7,199,122, plus a patent application in Canada, and Mexico. U.S. patent 4,138,487, assigned to Rhone-Poulenc Industries, claiming Oltipraz as a composition of matter, has expired.