ZNL-8162(ZNL-8162) - 药物靶点：MKK7_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

MKK7

作用机制

MKK7调节剂(mitogen-activated protein kinase kinase 7 modulators)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Stanford University

在研机构

Stanford University

非在研机构-

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 ZNL-8162 相关的临床结果

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100 项与 ZNL-8162 相关的转化医学

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100 项与 ZNL-8162 相关的专利（医药）

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1

项与 ZNL-8162 相关的文献（医药）

2024-06-26·ACS Central Science

Molecular Bidents with Two Electrophilic Warheads as a New Pharmacological Modality

Article

作者: Li, Zhengnian ; Eck, Michael J. ; Zhang, Tinghu ; Jiang, Jie ; To, Ciric ; Ficarro, Scott B. ; Marto, Jarrod A. ; Zhu, Yingde ; Li, Jiaqi ; Jänne, Pasi A. ; Gray, Nathanael S. ; Tavares, Isidoro ; Beyett, Tyler S. ; Che, Jianwei

A systematic strategy to develop dual-warhead inhibitors is introduced to circumvent the limitations of conventional covalent inhibitors such as vulnerability to mutations of the corresponding nucleophilic residue. Currently, all FDA-approved covalent small molecules feature one electrophile, leaving open a facile route to acquired resistance. We conducted a systematic analysis of human proteins in the protein data bank to reveal ∼400 unique targets amendable to dual covalent inhibitors, which we term "molecular bidents". We demonstrated this strategy by targeting two kinases: MKK7 and EGFR. The designed compounds, ZNL-8162 and ZNL-0056, are ATP-competitive inhibitors that form two covalent bonds with cysteines and retain potency against single cysteine mutants. Therefore, molecular bidents represent a new pharmacological modality with the potential for improved selectivity, potency, and drug resistance profile.

100 项与 ZNL-8162 相关的药物交易

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