Fragment-Based Screening Identifies Novel Non-Amino Acid Inhibitors of the Sodium-Coupled Neutral Amino Acid Transporter SNAT2.

ABSTRACT:

Introduction

Amino 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.

Methods

320 fragment compounds were screened for their inhibition of ³H-Gly uptake in hyperosmotically upregulated SNAT2-expressing PC-3 cells. The top five hits were studied further for their inhibitory potency and structure-activity re

SUBMITTER: Jakobsen S 

PROVIDER: S-EPMC12405023 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature