Synonyms: 4-(4-Isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide; 4-[2,5-Dihydro-2,3-dimethyl-4-(1-methylethyl)-5-oxo-1H-pyrazol-1-yl]-N-(2-phenoxyethyl)benzenesulfonamide
Molecular Formula: C22H27N3O4S
Molecular Weight: 429.53
Linear Structural Formula: C22H27N3O4S
Purity: >=98% (HPLC)
Storage: 2-8C
Biochem Physiol Actions: BC-LI-0186 is a selective blocker of Leucyl-tRNA synthetase (LRS; LeuRS) and Ras-related GTP-binding protein D (RagD) interaction (IC50 = 46.11 nM) by competing against RagD for LRS VC domain binding (KD = 42.1 nM) without affecting LRS-Vps34, LRS-EPRS, RagB-RagD association, mTORC1 complex formation or the activities of 12 kinases. BC-LI-0186 inhibits Leu-dependent LRS lysosomal membrane localization (10 muM), RagD GTPase and mTORC1 activation (IC50 = 81.4 nM against Leu-induced S6K phosphorylation), but not ARF1 activation, AKT S473 phosphorylation, Glu- or Arg-dependent S6K phosphorylation, nor the cytosolic and mitochondrial LRS catalytic activities. BC-LI-0186 effectively suppresses the growth of rapamycin-resistant MCT116 MM cancer cells with mTOR-S2035I mutation both in cultures (GI50 = 42.03) and in mice in vivo (by 40% in 2 wks; 20 mg/kg/day i.p.).