Galactose Kinase (GALK) Inhibitors for the Treatment of Galactosemia and Other Disorders of Galactose Metabolism

This technology includes selective inhibitors of the human enzyme galactokinase (EC 2.7.1.6), which may be useful for the treatment of Galactosemia and other diseases caused by aberrant galactose metabolism, including cancer. These compounds inhibit the first step in galactose metabolism, thereby eliminating the build-up of toxic metabolites during the aberrant metabolism of galactose, as well as inhibitor the entry of galactose into glycolysis and other downstream assays. Classic Galactosemia is a potentially lethal disorder with a high mortality rate when left untreated; our galactokinase inhibitors could provide the first therapeutic treatment for this disorder. Additionally, GALK1 is necessary for the survival of PTEN/AKT mis-regulated cancers, which consist of a large number of cancers studied to date. We have shown that our compounds can selectively kill cancer cells harboring these mutations as well as those with high expression levels of GALK.