Short Chain Fatty Acid (SCFA) - Carbohydrate Bifunctional Hybrid Molecules with Novel Anti-cancer Properties

Butyrate, a natural short chain fatty acid (SCFA), is well-established to have anti-cancer properties via its ability to induce cell cycle arrest and apoptosis in cancer cells. Currently, several clinical trials are underway for treatment of cancer (leukemia, prostate, sickle cell ulcers and liver disorder) with butyrate and its analogs. There have been several attempts to develop prodrugs for butyrate in the form of esters with innocuous carrier molecules like lactic acid, glycerol, glucose, mannose, galactose (etc.,) to improve the pharmacological properties (rapid clearance and high dosage) of the sodium butyrate. In this invention we have developed a panel of novel sugar-based butyrate carrying small-molecules that facilitate the efficient delivery of butyrate to their site of action within cells and, importantly, also contain a pro-active carrier moiety that works synergistically to enhance the induction of apoptosis in cancer cells. Background This invention greatly improves the efficiency by which butyrate, a potential anti-cancer drug, is used by human cells. The strategy of employing hydroxyl esters, and even sugars, as carrier molecules for the therapeutic delivery of butyrate has been reported previously. The key advance in this invention is that the sugar is specifically designed to fine-tune the cellular response of butyrate for various applications which is in contrast to previous efforts where the carbohydrate was essentially inert with respect to evoking a response for a biochemical pathway within a cell. To accomplish this objective, we have made novel specific sugar-butyrate hybrid molecules that have not been reported previously. Consequently, we have a new method to treat cancer cells (i.e., by making butyrate-sugar hybrid molecules where both moieties are important for giving a particular cellular response ? the sugar modulates glycosylation and the butyrate elicits fatty acid responses). Description (Set) Proposed Use (Set) This invention can be used to fine tune the desired pharmacological properties of butyrate, an anti-cancer drug.

Inventor(s): Yarema, Kevin J.

Type of Offer: Licensing

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