ZCL-039(ZCL-039) - 药物靶点：LeuRS_在研适应症：细菌性肺炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

LeuRS

作用机制

LeuRS抑制剂(亮氨酰-tRNA合成酶抑制剂)

治疗领域

感染呼吸系统疾病

在研适应症

细菌性肺炎

非在研适应症-

原研机构

Shanghai Institutes for Biological Sciences CAS

在研机构

Shanghai Institutes for Biological Sciences CAS

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-

关联

100 项与 ZCL-039 相关的临床结果

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100 项与 ZCL-039 相关的转化医学

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100 项与 ZCL-039 相关的专利（医药）

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1

项与 ZCL-039 相关的文献（医药）

Scientific Reports3区 · 综合性期刊

Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase

3区 · 综合性期刊

ArticleOA

作者: Zhi-Peng Fang ; Hu-Chen Zhou ; Jiong Zhang ; Meng Wang ; Qing-Hua Hu ; Wei Pan ; En-Duo Wang ; Ying-Ying Ding ; Ru-Juan Liu ; Min Tan

Streptococcus pneumoniae causes bacterial pneumonia with high mortality and morbidity. The emergency of multidrug-resistant bacteria threatens the treatment of the disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in cellular translation and is an attractive drug target for antimicrobial development. Here we report the compound ZCL039, a benzoxaborole-based derivative of AN2690, as a potent anti-pneumococcal agent that inhibits S. pneumoniae LeuRS (SpLeuRS) activity. We show using kinetic, biochemical analyses combined with the crystal structure of ZCL039-AMP in complex with the separated SpLeuRS editing domain, that ZCL039 binds to the LeuRS editing active site which requires the presence of tRNA(Leu), and employs an uncompetitive inhibition mechanism. Further docking models establish that ZCL039 clashes with the eukaryal/archaeal specific insertion I4ae helix within editing domains. These findings demonstrate the potential of benzoxaboroles as effective LeuRS inhibitors for pneumococcus infection therapy, and provide future structure-guided drug design and optimization.

100 项与 ZCL-039 相关的药物交易

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