Novel Inhibitors of the Amino Acid Transporters ASCT1 and ASCT2

The invention features compounds and methods relating to novel hydroxy-proline analog inhibitors of the ASCT1 and ASCT2 neutral amino acid transporters. These analogs are potent and selective inhibitors of ASCT2 and ASCT1-mediated amino acid transport as evidenced by significantly reduced glutamine or alanine transport-associated currents or radiolabeled substrate (amino acid) uptake in Xenopus oocytes expressing ASCT2 or ASCT1. Selectivity has been established in the same manner whereby reduced substrate associated current or substrate uptake is unobserved in Xenopus oocytes expressing ATA2, SN1, or EAAT(s) (excitatory amino acid transporter). The compounds and methods of the invention can be used in research or clinical applications (e.g., for the treatment of cancer, microbial infection, or ischemia-related central nervous system injury).