相关实验视频

Updated: Jun 13, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

发现和描述强效,选择性和口服生物可用的7-阿赞达AXL受体氨酸激酶抑制剂

Corinne N Foley¹, Shiwei Qu¹, Srinivas Reddy Paladugu¹

¹Arcus Biosciences, Inc., Hayward, California 94545, United States.

Journal of medicinal chemistry

|May 23, 2025

概括

研究人员开发了新的AXL抑制剂,以对抗癌症药物耐药性. 一种化合物AB801显示出临床开发的前景,为AXL驱动的癌症提供了一个新的治疗策略.

科学领域:

在瘤学瘤学.
药用化学医学化学
药理学药理学是指药理学的学科.

背景情况:

受体氨酸激酶 (AXL) 的高表达与各种癌症的不良预后和治疗耐药性相关.
准AXL是一种潜在的策略,可以克服对标准癌症疗法的耐药性.
现有的AXL抑制剂在阻断瘤信号传递方面的治疗窗口和有效性尚不清楚.

研究的目的:

设计和优化基于7-azainazole的新型AXL抑制剂.
确定一种工具化合物,用于在体内验证AXL抑制.
发现一种具有改善性质的临床开发候选物来治疗AXL驱动的癌症.

主要方法:

结构-活性关系 (SAR) 研究指导了7-azainazole衍生物的优化.
在体内进行的研究使用一种工具化合物来评估抗瘤疗效.
优化专注于实现所需的效能,选择性,生物可用性和安全性.

主要成果:

成功开发了一系列新的7-azainazole AXL 抑制剂.
一种优化的工具化合物在组合治疗中显示出显著的瘤体积减少.
化合物68表现出良好的功效,基因组选择性,口服生物可用性和安全性.
通过进一步优化,确定了临床开发候选人AB801.

结论:

由SAR驱动的优化产生了强效和选择性的AXL抑制剂.
开发的化合物,包括AB801,代表了针对AXL相关癌症的有前途的治疗药物.
这项研究为在临床环境中推进针对AXL的治疗提供了基础.

更多相关视频

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...