ZK-53(ZK-53) - 药物靶点：CLPP_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

CLPP

作用机制

CLPP激动剂(caseinolytic mitochondrial matrix peptidase proteolytic subunit agonists)

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

中国科学院上海药物研究所

在研机构

中国科学院上海药物研究所

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)临床前

特殊审评-

结构

分子式C19H20BrF2N3O

InChIKeyHRSJZGGIFGZVFD-UHFFFAOYSA-N

CAS号3031789-26-8

关联

100 项与 ZK-53 相关的临床结果

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100 项与 ZK-53 相关的转化医学

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100 项与 ZK-53 相关的专利（医药）

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1

项与 ZK-53 相关的文献（医药）

Nature Communications1区 · 综合性期刊

Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma

1区 · 综合性期刊

ArticleOA

作者: Wang, Pengyu ; Yue, Chuan ; Xue, Yun ; Pan, Yihui ; Li, Meixia ; Gan, Jianhua ; Zhou, Lin-Lin ; Zhang, Tao ; Ji, Hongbin ; Yang, Cai-Guang ; Yang, Teng ; Ding, Kan ; Zhou, Hu

AbstractChemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a π-π stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones. ZK53 treatment causes a decrease of the electron transport chain in a ClpP-dependent manner, which results in declined oxidative phosphorylation and ATP production in lung tumor cells. Mechanistically, ZK53 inhibits the adenoviral early region 2 binding factor targets and activates the ataxia-telangiectasia mutated-mediated DNA damage response, eventually triggering cell cycle arrest. Lastly, ZK53 exhibits therapeutic effects on lung squamous cell carcinoma cells in xenograft and autochthonous mouse models.

100 项与 ZK-53 相关的药物交易

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