ArticlePharmaceutical research2025
Fragment-Based Screening Identifies Novel Non-Amino Acid Inhibitors of the Sodium-Coupled Neutral Amino Acid Transporter SNAT2.
Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionAmino acid transporters like the sodium-coupled neutral amino acid transporter 2 (SNAT2, SLC38A2) have gained interest for their roles in, e.g., the central nervous system and in cancer. Efforts in discovering inhibitors against these transporters often result in amino acid-based inhibitors that lack selectivity and are likely to compete with amino acid substrates to bind their targets. To circumvent this, we aimed to discover novel non-amino acid inhibitors of SNAT2 by screening a library of fragment-sized compounds.
methods320 fragment compounds were screened for their inhibition of
resultsThe screen revealed two similar scaffolds that showed SNAT2 inhibition, namely 1,3-benzothiazole-2-amine and 1,3-benzoxazole-2-amine. The SAR revealed how hydrophobic substituents at specific positions were needed for the structures to show SNAT2 inhibition. The best inhibitors inhibited SNAT2 with IC
conclusionIn conclusion, we discovered multiple novel non-amino acid compounds that inhibited SNAT2 and can serve as starting points for the further development of SNAT2 inhibitors.
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