BC-LI-0186 是一种有效的选择性亮氨酸 tRNA 合成酶 (Leucyl-tRNA synthetase (LRS)) 与 Ras 相关的 GTP 结合蛋白 D (RagD) 相互作用的抑制剂 (IC₅₀=46.11 nM)。BC-LI-0186 与 LRS 的 RagD 相互作用位点 (K_d=42.1 nM) 竞争，并对 LRS- vps34、LRS- eprs、RagB-RagD 缔合、mTORC1 复合物的形成没有产生影响。BC-LI-0186 能有效抑制肿瘤相关 MTOR 突变体的活性和雷帕霉素耐药癌细胞的生长。BC-LI-0186 可用于肺癌的相关研究。

BC-LI-0186 is a potent and selective inhibitor of Leucyl-tRNA synthetase (LRS; LeuRS) and Ras-related GTP-binding protein D (RagD) interaction (IC 50 =46.11 nM). BC-LI-0186 competitively binds to the RagD interacting site of LRS (K d =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.

Solid

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

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 (H

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.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[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.

In Vitro: DMSO : 125 mg/mL (291.02 mM; Need ultrasonic)配制储备液