Pharmacological and structural insights into nanvuranlat, a selective LAT1 (SLC7A5) inhibitor, and its N-acetyl metabolite with implications for cancer therapy.

ABSTRACT: L-type amino acid transporter 1 (LAT1, SLC7A5), overexpressed in various cancers, mediates the uptake of essential amino acids crucial for tumor growth. It has emerged as a promising target for cancer therapy. Nanvuranlat (JPH203/KYT-0353), a LAT1 inhibitor, has shown antitumor activity in preclinical studies and efficacy in biliary tract cancer during clinical trials. This study provides a comprehensive pharmacological characterization of nanvuranlat and its N-acetyl metabolite, including structural insights into their LAT1 interactions. Both compounds demonstrated high selectivity for LAT1 over LAT2 and other amino acid transporters. Nanvuranlat acts as a competitive, non-transportable LAT1 inhibitor (K_i = 38.7 nM), while its N-acetyl metabolite retains selectivity but with re

SUBMITTER: Jin C 

PROVIDER: S-EPMC11758009 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature