BC-LI-0186

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.

Product information

CAS Number: 695207-56-8

Molecular Weight: 429.53

Formula: C22H27N3O4S

Chemical Name: 4-[2,3-dimethyl-5-oxo-4-(propan-2-yl)-2,5-dihydro-1H-pyrazol-1-yl]-N-(2-phenoxyethyl)benzene-1-sulfonamide

Smiles: CN1C(C)=C(C(C)C)C(=O)N1C1C=CC(=CC=1)S(=O)(=O)NCCOC1C=CC=CC=1

InChiKey: SQYWMHPZMHDCHP-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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). 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. 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. 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).

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.

Products are for research use only. Not for human use.