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).  Inhibition of these proteins disrupts the intricate ion balances within cancer cells to a much greater extent than in normal cells, and this leads to 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 have synthesized prodrug forms of potent NHE inhibitors to address the drug delivery challenge.  Our synthetic efforts and biological activities will be discussed.

Prodrugs for sodium-proton exchange inhibition: Targeting brain cancer cells

239th National Meeting (2010)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.