2-B-SS12-4 〇西窪 航¹、大垣 隆一^1,2、岡西 広樹¹、徐 旻憓¹、遠藤 仁³、金井 好克^1,2 Kou Nishikubo¹, Ryuichi Ohgaki^1,2, Hiroki Okanishi¹, Minhui Xu¹, Hitoshi Endou³, Yoshikatsu Kanai^{1,2 1}大阪大・院医・生体システム薬理、²大阪大・先導的学際研究機構・生命医科学融合フロンティア研究部門、³ジェイファーマ株式会社 ¹Dept. Bio-system Pharmacol., Grad. Sch. Med., Osaka Univ., ²Integ. Front. Res. Med. Sci. Div., OTRI, Osaka Univ., ³J-Pharma Co., Ltd. Nanvuranlat (JPH203, KYT-0353), an inhibitor for L-type amino acid transporter 1 (LAT1; SLC7A5), suppresses the cancer cell proliferation and tumor growth by inhibiting the uptake of large neutral amino acids into cancer cells. Most previous studies have focused on the inhibition of leucine uptake to describe the pharmacological effects of nanvuranlat, mainly because leucine is an essential amino acid that functions as activating signaling molecules of cellular metabolism. In this study, to elucidate the anti-cancer effects of LAT1 inhibitors in more detail, we focused on changes in the intracellular concentrations of all the LAT1 substrates and their importance on cell proliferation. Surprisingly, high-performance liquid chromatography analysis revealed that only three large neutral amino acids were continuously decreased by the treatment with nanvuranlat. Similar changes were commonly observed in multiple cancer cell lines. Culturing the cells in media depleted with each or all of the three amino acids reduced the intracellular amount of corresponding amino acids, partially recapitulating the effects of nanvuranlat on cell proliferation, amino acid signaling, and cell cycle arrest. These findings contribute to understanding the molecular basis underlying the anti-cancer effects of LAT1 inhibitors.