Publication Date

2024

Document Type

Book

Description

Nitrogen is an important element that exists in many biological compounds essential for the cells’ survivability. Due to rapid growth and proliferation, cancer cells demand large amounts of nitrogen, specifically from glutamine. ASCT2 transporters are found to be overexpressed in many types of cancers. The inhibition of ASCT2 is proposed to induce cell starvation. EAAT1 (SLC1A3) and ASCT2 (SLC1A5) exhibit similar allosteric inhibition mechanisms. Previous experiments showed that UCPH-101 allosterically binds to EAATs and inhibits their translocation activity. While the mechanism is unknown, the molecule was shown to be a partial inhibitor of ASCT2. We hypothesized that alteration of the side chain of UCPH-101 is expected to lead to different inhibition constants (Ki) and percentages of the molecules on ASCT2 and the inhibition mechanism of UCPH-101 can be obtained from inhibition studies using UCPH derivatives. These inhibitors are chemically synthesized, characterized using patch-clamp electrophysiology, and tested using cytotoxicity assay.

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Synthesis and Characterization of Derivatives of UCPH-101 as Novel Inhibitors Targeting SLC1 Amino Acid Transporter Family

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