Inhibitors of Heparan Sulfate Biosynthesis and Cancer

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DESCRIPTION (provided by applicant): The underlying hypothesis of this proposal is that inhibitors of heparan sulfate biosynthesis will slow tumor growth. Genetic and pharmacological data has validated heparan sulfate as a novel anti-cancer target. This proposal describes a drug discovery program that uses two high throughput cell-based screens to identify small molecule inhibitors of heparan sulfate biosynthesis. Both assays have been validated through their ability to detect partial inhibition of heparan sulfate by chlorate, an inhibitor of macromolecular sulfation. This proposal requests funds to run the high throughput discovery screen and to characterize the lead molecules that emerge. In vitro testing of the effects on growth factor signaling will be used to determine if the compounds represent viable drug development candidates. Promising leads will be candidates for further development as novel anti-cancer drugs in a Phase II SBIR application.