Towards the Development of Alanine Serine Cysteine Transporter 2-Selective Inhibitors and Molecular Probes to Interrogate Cancer Metabolism

Abstract

ASCT-2 is an evolutionary redundant neutral amino acid transporter protein that has been consistently reported as being expressed at elevated levels in high profile malignant diseases, such as breast, lung, and gastrointestinal cancers. Its role in cancer metabolism has been elucidated as a primary and selective transporter of L-glutamine, an endogenous substrate utilized as a nitrogenous source of fuel used to sustain high cellular proliferation rates. ASCT-2 over-expression has been linked with high-mortality diseases, including breast and colorectal cancers, attributed to advanced tumor development. The important role of ASCT-2 as a major contributor to glutamine intake, in cancer metabolism, presents a unique opportunity for medicinal development of novel therapeutics in selectively targeting ASCT-2 inhibition and remediate tumor growth. This work entails a medicinal campaign towards the discovery and development of novel pharmaceuticals for the inhibition of ASCT-2 mediated glutamine uptake.