Relative to healthy brain tissue, the heightened metabolism of cancer cells increases their reliance on the ion transport proteins NHE (sodium-proton exchanger) and NCX (sodium-calcium exchanger). Recently, we have shown that dual NHE/NCX inhibition causes non-apoptotic brain cancer cell death. In contrast, healthy brain cells are less affected by this targeted approach because they are far less reliant on NHE/NCX due to their normal metabolic activity. Consequently, NHE and NCX are excellent molecular targets for a new, selective brain cancer therapy. Although potent NHE/NCX inhibitors are available, a fundamental impediment is the delivery of these compounds to poorly vascularized tissues. As part of our target-specific approach to treating brain cancer, we are synthesizing prodrug forms of potent NHE and NCX inhibitors to address the drug delivery challenge. Our synthetic efforts and preliminary biological activities will be discussed.

Prodrugs for cell surface ion exchange inhibition: Targeting brain cancer cells

243rd National Meeting (2012)

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