Sustained reductions in valine and isoleucine mediate anti-cancer pharmacological effects of inhibiting amino acid transporter LAT1 in cancer cells.

ABSTRACT:

Background

L-type amino acid transporter 1 (LAT1; SLC7A5), which preferentially transports large neutral amino acids (LNAAs), is highly upregulated in various cancers and represents a promising therapeutic target. The first-in-class LAT1-specific inhibitor, nanvuranlat (JPH203, KYT-0353), has exhibited potent anti-cancer effects and is under clinical evaluation. However, alterations in the amino acid availability in cancer cells underlying its pharmacological activities remain to be elucidated.

Methods

Amino acids in nanvuranlat-treated cancer cells were measured by high-performance liquid chromatography. LAT1 knockdown was performed using siRNA. To mimic LAT1 inhibition, cancer cells were incubated in culture media lacking specific LNAA(s) reduced by nanvuranlat. The conseq

SUBMITTER: Nishikubo K 

PROVIDER: S-EPMC12673697 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature