ProTide NUC-7738: Anti-Cancer Properties of Cordycepin Improved by a New Process

Cordycepin the active ingredient in a Tibetan mushroom combined with advanced biotechnology has led to the development of a new treatment for cancer. A study by researchers at the University of Oxford showed that the anti-cancer effects of cordycepin can be improved using technology that prevents degradation in vivo.

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An unusual fungus that grows in the Tibetan highlands more than 3,500 meters above sea level Cordyceps Sinensis also known as caterpillar fungus is an ascomycete that is an endoparasite of lepidopteran larvae, which it kills to develop in their bodies. It has been highly valued in traditional Chinese medicine for centuries for its aphrodisiac and tonic properties and for the treatment of respiratory and kidney diseases and is now used as a dietary supplement due to its beneficial health effects.

Cordycepin: a nucleotide analog against cancer

This mushroom contains a substance, cordycepin, which has been recognized in various publications as an immunomodulator and antioxidant. This natural nucleoside analog has also been identified for its anticancer action by inducing apoptosis of tumor cells in vitro in a mouse cancer model. In addition, this compound has an anti-metastatic effect (inhibiting the invasive nature of cancer cells).

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Nucleoside analogs are now commonly prescribed as cancer chemotherapies. By giving cancer cells building blocks of defective DNA and RNA, they block their multiplication and lead to cancer cells’ death.

Unfortunately, resistance mechanisms to these compounds exist in tumors, and cordycepin, despite its potent effects in vitro, has reduced activity in vivo due to its rapid degradation by enzymes in the bloodstream and poor absorption by the cells.

Making cordycepin more effective

In collaboration with a biopharmaceutical company, researchers at the University of Oxford used a process that involves chemically embedding a protective sheath into the cordycepin. Once inside the cancer cells, this sheath is destroyed, releasing the active substance. This technology, called ProTide, is already being used to overcome the limitations of nucleotide analogs, particularly in antiviral treatments.

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In this Phase I clinical trial, researchers showed that NUC-7738 (the ProTide form of cordycepin) is 7 to 40 times more potent than the natural drug on cancer cells. The results showed that it resists degradation by circulating enzymes and releases the active anti-cancer metabolite into the cells effectively. It is well tolerated and shows encouraging signs of antitumoral activity in patients with advanced solid tumors. The combination of an anticancer agent such as cordycepin and novel technology that circumvents the resistance mechanisms involved in the degradation during transport and activation of the active ingredient offers new perspectives. A phase II study is underway to determine the recommended dose.


The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trial



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