BC-LI-0186 is a selective blocker of Leucyl-tRNA synthetase (LRS, LeuRS) and Ras-related GTP-binding protein D (RagD) interaction (LRS-RagD interaction) (IC50 = 46.11 nM) by competing against RagD for LRS VC domain binding (KD = 42.1 nM), thereby inhibiting lysosomal localization of LRS and mTORC1 activity. It also effectively suppresses the activity of cancer-associated mTOR mutants and the growth of rapamycin-resistant cancer cells.