Advances in the development of large neutral amino acid transporter 1 (LAT1) substrate analogues and inhibitors for the delivery of drugs and radiopharmaceuticals.

Large neutral amino acid transporter 1 (LAT1) is a family of transmembrane proteins that recognize and transport large neutral amino acids. Overexpression of LAT1 has been implicated in the pathogenesis of diverse cancers, primarily owing to its role in facilitating the cellular uptake of essential amino acids for tumour growth. Consequently, pharmacological intervention targeting LAT1 functionality has emerged as a therapeutically promising approach for cancer treatment. This review elaborates on the structural characteristics and biological activities of diverse LAT1-targeting compounds, including natural and synthetic amino acid derivatives. Additionally, radionuclides are attached to LAT1 inhibitors and utilized in tumour targeted therapy and imaging. In this review, small molecular LAT1 inhibitors/radiopharmaceuticals developed over the past 15 years are comprehensively overviewed.