BC-LI-0186 是一种有效的选择性亮氨酰-tRNA 合成酶 (LRS; LeuRS) 和 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 竞争性结合 LRS 的 RagD 相互作用位点 (Kd=42.1 nM)，并影响 LRS-Vps34、LRS-EPRS、RagB-RagD 结合、mTORC1 复合物形成或 12 种激酶的活性。 BC-LI-0186 可以有效抑制癌症相关的 MTOR 突变体的活性和雷帕霉素耐药癌细胞的生长。 BC-LI-0186 是一种很有前途的肺癌研究药物。
货号:ajcx27818
CAS:695207-56-8
分子式:C22H27N3O4S
分子量：429.54
溶解度:Soluble in DMSO
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Potent and high affinity leucyl-tRNA synthase (TRS)/Ras-related GTP-binding protein D (RagD) interaction inhibitor (IC50 = 46.1 nM; Kd = 42.1 nM for binding to LRS). Inhibits mTOR complex 1 activity by blocking binding to LRS without affecting catalytic activity. Inhibits leucine-induced translocation of LRS to the lysosome.

Kim et al (2017) Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction. Nat.Commun. 8 732 PMID:28963468 |Choi et al (2017) Leucine-induced localization of Leucyl-tRNA synthetase in lysosome membrane. Biochem.Biophys.Res.Commun. 493 1129 PMID:28882589 |Lee et al (2018) Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway. Proc.Natl.Acad.Sci.USA. 115 E5279 PMID:29784813