Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
Transporters are membrane proteins that contribute to the distribution of compounds in the body. Drugs that target them can achieve various metabolic regulations. In the cells involved in pathogenesis, such as cancer cells, changes in the metabolic system due to metabolic reprogramming often play an essential role in maintaining their function and survival. In particular, nutrient transporters that contribute to the regulation of cellular metabolism can be targets for drugs that intervene in intracellular metabolism and prevent the development of pathological states. We discovered the amino acid transporter LAT1 (SLC7A5), upregulated in cancer cells. We revealed that it contributes to maintaining cancer cell-specific functions through the amino acid signaling centered on mTORC1. Inhibitors generated based on the structure-activity relationship analysis showed antitumor effects and regulated the function of cells other than cancer cells that express LAT1 in the course of pathogenesis, such as vascular endothelial cells and immune cells. In addition, the structure of LAT1 was recently elucidated by cryo-EM, showing the mechanism of substrate recognition and action of inhibitors. In this lecture, the role of transporters in metabolic reprogramming revealed by LAT1 inhibitors and the significance of LAT1 as a drug discovery target will be discussed.
