1. Metabolic Enzyme/Protease
  2. Aminoacyl-tRNA Synthetase
  3. BC-LI-0186

BC-LI-0186 

Cat. No.: HY-136265
Handling Instructions

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 competively 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.

For research use only. We do not sell to patients.

BC-LI-0186 Chemical Structure

BC-LI-0186 Chemical Structure

CAS No. : 695207-56-8

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Description

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 competively 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].

IC50 & Target

IC50: 46.11 nM (LeuRS and RagD interaction)[1]
Kd: 42.1 nM (LeuRS and RagD interaction)[1]

In Vitro

BC-LI-0186 (0-20 μM; starved for 90 min in the leucine-free medium and then in the serum-free media for 15 min) inhibits phosphorylation of S6K in a dose- and time-dependent manner, but it has no effects on hosphorylation of AKT (S473)[1].
BC-LI-0186 (0-20 μM; 6 hours) induces cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 and an increase of p62 in A549 and H460 cells[1].
BC-LI-0186 exhibits cytotoxic effect at nanomolar concentration in NSCLC cells, it exhibits IC50 values of 98 nM, 206 nM, 55 nM, 78 nM, 83 nM, 86 nM, 102  nM, 109 nM, 128 nM, and 206 nM in A549, H460, H2228, H1703, SNU1330, H1650, H2009, H358, H2279, H460, and H596 cells, respectively[1].
BC-LI-0186 overcome acquired rapamycin resistance and inhibits the mTORC1 pathway in isogenic HCT116 cell lines that harbored either M TOR WT (HCT116 MW) or S2035I mutations (HCT116 MM), it exhibits little changed efficacy between the wild-type and mutant cells (GI50: 39.49  nM and 42.03 nM, EC50: 105.03 nM and 100.45  nM)[1].

Cell Viability Assay[1]

Cell Line: NSCLC cells
Concentration: 0 μM, 0.1 μM, 0.2 μM,1 μM, 2 μM, 5 μM, 10 μM, 20 μM
Incubation Time: Starved for 90 min in the leucine-free medium and then in the serum-free media for 15 min
Result: Suppressed leucine-mediated mTORC1 activation in NSCLC cells.
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.
Molecular Weight

429.53

Formula

C₂₂H₂₇N₃O₄S

CAS No.

695207-56-8

SMILES

O=S(C1=CC=C(N2N(C)C(C)=C(C(C)C)C2=O)C=C1)(NCCOC3=CC=CC=C3)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

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Keywords:

BC-LI-0186Aminoacyl-tRNA SynthetasetRNA Synthetase, aaRSLeucyl-tRNA synthetaseRagDrapamycin-resistantlung cancerA549H460KRAS G12DInhibitorinhibitorinhibit

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