Hitgen, Inc.

Jingchao Feng

Jin Li

Dengyou Zhang

Hongmei Song

Guoqing Zhong

Yan Zhang

Jinqiao Wan

Dengfeng Dou

Wei Chen

Jing Hu

Xiao Hu

Zhi Wang

Wei Liao

Xing Wang

Si Li

Leichang Pan

Benyanzi Yang

Li Lin

Xiaohu Ge

Disclosed is a macrocyclic kinase inhibitor, wherein the compound, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is as shown in formula I. Experiments show that the new compound as shown in formula I disclosed in the present invention exhibits an excellent TRK inhibitory activity, has a significant inhibitory effect on TRKA-mutant cell growth, and exhibits an excellent inhibitory effect on in vivo tumor growth, thus providing a new choice for the clinical treatment of diseases associated with abnormal TRK activity.

Macrocyclic kinase inhibitor

Disclosed herein are a compound of formula (I) and a preparation method and uses thereof. The compound shows a good inhibitory activity against ROCK, providing a new medicinal strategy to clinically treat the diseases associated with abnormal ROCK activity. 

Rock-inhibiting compound and uses thereof

The present invention discloses a method for capturing drug targets, comprising the following steps of: (1) preparing row materials, i.e., compounds and DNA or RNA or one party of other specific affinity materials; (2) linking: covalently linking the compounds to the DNA or RNA or the one party of other specific affinity materials, to obtain labeled compounds; (3) transferring: transferring the labeled compounds obtained in the step (2) into cells by a specific gene transfer method; (4) capturing targets: disrupting the cells in the step (3), and then capturing the DNA or RNA in the step (1) by immobilized complementary DNA or RNA, or capturing the one party of affinity materials in the step (1) by the other party of immobilized specific affinity materials, thus to enrich the targets through the covalently linked labeled compounds and the affinity of the targets; (5) identifying targets: dissociating the enriched targets from a stationary phase, deploying the targets by a gel electrophoresis method or by an equivalent separation method, and comparing differential proteins by proteomics thus to identify the potential targets; and (6) determining targets: expressing or purchasing the targets identified in the step (5) by priority, and comparing by interaction of the compounds with those targets one by one to determine the targets for the compounds. By the method of the present invention, compounds with low membrane permeability may be transferred into cells to be bound with the targets in the cells, to realize the target identification closer to the real physiological environment and thus provide more conclusive evidences for the acting mechanism of the compounds to diseases. Additionally, the method for capturing drug targets of the present invention is novel, easy, efficient, and low in cost, and has good application prospects.

Drug target capturing method

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Sichuan, China

Jingchao Feng