| Identification | Back Directory | [Name]
4-(2,3-dimethyl-5-oxo-4-propan-2-ylpyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide | [CAS]
695207-56-8 | [Synonyms]
BC-LI-0186
3-dimethyl-5-oxo-4-propan-2-ylpyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide
4-(2,3-dimethyl-5-oxo-4-propan-2-ylpyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide
4-(4-Isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide
Aminoacyl-tRNA Synthetase,RagD,rapamycin-resistant,BCLI0186,tRNA Synthetase, aaRS,H460,KRAS G12D,A549,lung cancer,BC LI 0186,inhibit,Inhibitor,Leucyl-tRNA synthetase | [Molecular Formula]
C22H27N3O4S | [MDL Number]
MFCD05259468 | [MOL File]
695207-56-8.mol | [Molecular Weight]
429.53 |
| Chemical Properties | Back Directory | [Boiling point ]
582.9±60.0 °C(Predicted) | [density ]
1.232±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
Solid | [pka]
10.68±0.50(Predicted) | [color ]
White to off-white | [InChI]
1S/C22H27N3O4S/c1-16(2)21-17(3)24(4)25(22(21)26)18-10-12-20(13-11-18)30(27,28)23-14-15-29-19-8-6-5-7-9-19/h5-13,16,23H,14-15H2,1-4H3 | [InChIKey]
SQYWMHPZMHDCHP-UHFFFAOYSA-N | [SMILES]
O=C(C(C(C)C)=C(C)N1C)N1C2=CC=C(S(NCCOC3=CC=CC=C3)(=O)=O)C=C2 |
| Hazard Information | Back Directory | [Uses]
BC-LI-0186 is a potent and selective inhibitor of Leucyl-tRNA synthetase (LRS; LeuRS) and Ras-related GTP-binding protein D (RagD) interaction (IC50=46.11 nM). BC-LI-0186 competitively binds to the RagD interacting site of LRS (Kd=42.1 nM) and has on effects on LRS-Vps34, LRS-EPRS, RagB-RagD association, mTORC1 complex formation or the activities of 12 kinases. BC-LI-0186 can effectively suppress the activity of cancer-associated?MTOR?mutants and the growth of rapamycin-resistant cancer cells.?BC-LI-0186 is a promising agent for lung cancer research[1][2]. | [Biological Activity]
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-Vps34LRS-EPRSRagB-RagD associationmTORC1 complex formation or the activities of 12 kinases. BC-LI-0186 inhibits Leu-dependent LRS lysosomal membrane localization (10 μM)RagD GTPase and mTORC1 activation (IC50 = 81.4 nM against Leu-induced S6K phosphorylation)but not ARF1 activationAKT S473 phosphorylationGlu- or Arg-dependent S6K phosphorylationnor 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.). | [in vivo]
BC-LI-0186 (intraperitoneal injection; 50 mg/kg; alone or combines with cisplatin alone; 2 weeks; bid for 5 days per week) exhibits antitumor effects and significantly reduces tumor size compared with treatment with vehicle in an LSL K-ras G12D lung cancer animal model[1]. | Animal Model: | K-ras mouse lung cancer modelan LSL K-ras G12D lung cancer animal model[1] | | Dosage: | 50?mg/kg | | Administration: | Intraperitoneal?injection; 50?mg/kg; alone or combines with cisplatin alone; 2 weeks; bid for 5?days per week | | Result: | Showed activated caspase-3-positive cells higher in the BC-LI-0186-treated group than in the vehicle or cisplatin-treated group.Reduced p-S6 and p-AKT level whereas cisplatin alone has minimal effect on both p-S6 and p-AKT expression.Showed a slight (not statistically significant) increase in body weight during the treatment period.Exhibited a specific inhibition of mTORC1 and not mTORC2. |
| [storage]
Store at -20°C | [References]
[1] Jong Hyun Kim, et al. Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction. Nat Commun. 2017 Sep 29;8(1):732. DOI:10.1038/s41467-017-00785-0 |
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1-631-485-4226; 16314854226 |
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