UNC-9435(UNC-9435) - 药物靶点：MerTK x TYRO3_在研适应症：非小细胞肺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

MerTK x TYRO3

作用方式

抑制剂

作用机制

MerTK抑制剂(Mer受体酪氨酸激酶抑制剂)、TYRO3抑制剂(TYRO3蛋白酪氨酸激酶抑制剂)

治疗领域

肿瘤呼吸系统疾病

在研适应症

非小细胞肺癌

非在研适应症-

原研机构

The University of North Carolina at Chapel Hill

在研机构

The University of North Carolina at Chapel Hill

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)-

特殊审评-

关联

100 项与 UNC-9435 相关的临床结果

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100 项与 UNC-9435 相关的转化医学

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100 项与 UNC-9435 相关的专利（医药）

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1

项与 UNC-9435 相关的文献（医药）

2025-04-24·Journal of Medicinal Chemistry

Discovery of Novel TYRO3/MERTK Dual Inhibitors

Article

作者: Zhou, Yubai ; Guduru, Shiva K. R. ; Yan, Dan ; Shelton Earp, H. ; Zhao, Jichen ; Frye, Stephen V. ; Kania, Catherine E. ; Stashko, Michael A. ; Kong, Deyu ; Huang, Daowei ; Graham, Douglas K. ; DeRyckere, Deborah ; Wang, Xiaodong ; Kireev, Dmitri ; Ding, Ransheng ; Huelse, Justus M.

The TAM (TYRO3, AXL, MERTK) family of receptor tyrosine kinases has roles in oncogenesis and innate immunity, but the relative importance of the family members can differ in different contexts and between tumor types or individual tumors. Dual TYRO3 and MERTK inhibition may be advantageous for treatment of diseases or in tumors that are dependent on their coordinated action. Here, we report the discovery of the first potent dual TYRO3/MERTK inhibitor, UNC9435 (44). UNC9435 has 46-fold and 120-fold selectivity of MERTK over AXL and FLT3, respectively, and selectively against a panel of 30 other kinases. TYRO3 and MERTK inhibitory activities were confirmed by NanoBRET assays in HEK293 cells, with <0.51 nM EC₅₀ values for both enzymes and >3000-fold selectivity over AXL. UNC9435 also inhibited TYRO3, MERTK, and downstream oncogenic signaling in cancer cells and reduced colony formation in non-small cell lung cancer cultures, indicating its potential as a novel cancer therapeutic.

100 项与 UNC-9435 相关的药物交易

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