Glycoconjugates of Antiproliferative Iron Pro-Chelators Targeting Cancer Cell Metabolism

This technology provides novel glycoconjugates of antiproliferative iron pro-chelators that target the altered metabolism of cancer cells.

The key to the success of chelation therapy in cancer treatment is the ability to target iron ions in malignant cells without affecting iron levels in the bloodstream and in normal tissues. Lacking such selectivity, currently available chelators have been found to elicit adverse side effects when employed in cancer research. The success of this technology centers on the iron pro-chelators with a glucose-targeting unit, allowing for selective targeting of malignant cells. By selectively depriving cancer cells of a key metal ion essential for their rapid proliferation, this approach could lead to the development of efficacious and safe anti-cancer therapeutic candidates.

Background:
Cancer cells require higher iron levels in order to sustain fast proliferation rates, and have high glucose demands to sustain growth. This vulnerability of malignant behavior can be targeted by the use of small-molecule chelators that interfere with the availability of intracellular iron. Because the ability to decrease iron levels offers an opportunity to slow or halt tumor growth, iron chelation is emerging as a potential anti-cancer therapeutic avenue. The key to success of chelation therapy in cancer treatment, however, is the capacity to target iron in malignant cells selectively over normal tissues and iron in the extracellular space. Lacking such selectivity, currently available iron chelators have elicited adverse side effects when employed in cancer research, and none of the iron chelators used for iron overload blood disorders have received approval for a cancer indication to date.

Advantages:

• The technology concurrently exploits physiological characteristics of malignant cells, offering therapeutic efficacy with reduced or minimal side effects
• This new generation of chelators disrupts cancer cell metabolism through selective iron deprivation
• This technology holds high promise for success by exploiting aspects of cancer physiology that are not targeted by current clinical chemotherapy, namely:
  • their marked glucose avidity; and
  • their susceptibility to iron deprivation

Applications:

• Cancer treatment