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ID: ALA3576761

Journal: Bioorg Med Chem Lett

Title: 2-Substituted Nγ-glutamylanilides as novel probes of ASCT2 with improved potency.

Authors: Schulte ML, Dawson ES, Saleh SA, Cuthbertson ML, Manning HC.

Abstract: Herein, we report the discovery and structure-activity relationships (SAR) of 2-substituted glutamylanilides as novel probes of the steric environment comprising the amino acid binding domain of alanine-serine-cysteine transporter subtype 2 (ASCT2). Focused library development led to three novel, highly potent ASCT2 inhibitors, with N-(2-(morpholinomethyl)phenyl)-L-glutamine exhibiting the greatest potency in a live-cell glutamine uptake assay. This level of potency represents a three-fold improvement over the most potent, previously reported inhibitor in this series, GPNA. Furthermore, this and other compounds in the series exhibit tractable chemical properties for further development as potential therapeutic leads.

CiteXplore: 25435145

DOI: 10.1016/j.bmcl.2014.10.098