L1Au2(L1Au2) - 药物靶点：EGFR x TrxR_在研适应症：肺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

EGFR x TrxR

作用方式

拮抗剂、抑制剂

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、TrxR抑制剂(硫氧还蛋白还原酶抑制剂)

治疗领域

肿瘤呼吸系统疾病

在研适应症

肺癌

非在研适应症-

原研机构

华中科技大学

在研机构

华中科技大学

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)临床前

特殊审评-

结构/序列

分子式C24H24AuClFN6O2P

InChIKeyTVXSJXAKCZETHP-UHFFFAOYSA-N

CAS号3038386-42-1

关联

100 项与 L1Au2 相关的临床结果

登录后查看更多信息

100 项与 L1Au2 相关的转化医学

登录后查看更多信息

100 项与 L1Au2 相关的专利（医药）

登录后查看更多信息

1

项与 L1Au2 相关的文献（医药）

2025-03-13·Journal of Medicinal Chemistry

Dual-Targeting TrxR-EGFR Alkynyl-Au(I) Gefitinib Complex Induces Ferroptosis in Gefitinib-Resistant Lung Cancer via Degradation of GPX4

Article

作者: Lu, Yunlong ; Wang, Lingling ; Liu, Xiansheng ; Liu, Huiguo ; Ma, Xiaoyan ; Liu, Wukun ; Wang, Yawen ; Zheng, Pengdou ; Zhou, Ling ; Wei, Shuang ; Luo, Miao

Gefitinib exhibits significant clinical efficacy in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) sensitive mutations. However, its efficacy is severely limited by acquired resistance. Herein, we designed and synthesized a series of dual-targeting thioredoxin reductase (TrxR)-EGFR gold complexes by attaching a gold ligand to the parent structure of gefitinib, 4-anilinoquinazoline. Among them, L1Au2 exhibited significant activity against both gefitinib-sensitive and resistant lung cancers, effectively inhibiting tumor proliferation and promoting apoptosis. Mechanistically, L1Au2 effectively inhibits TrxR and EGFR both in vitro and in vivo. Additionally, L1Au2 promotes the degradation of GPX4 protein via autophagolysosomal and proteasomal pathways, leading to ferroptosis. Notably, L1Au2 also induces endoplasmic reticulum stress (ERS) and triggers immunogenic cell death (ICD). In conclusion, this study provides an innovative strategy for overcoming gefitinib resistance in lung cancer by utilizing dual-targeting TrxR-EGFR alkynyl-Au(I) gefitinib derivatives, thereby offering a new approach for treating gefitinib-resistant lung cancer.

100 项与 L1Au2 相关的药物交易

登录后查看更多信息