交互Traf2和Nck的激酶抑制剂:专利审查 (2008年至2024年)
Luoheng Qin1, Vladimir Aladinskiy2, David Gennert3
1Insilico Medicine Shanghai Ltd, Shanghai, China.
Expert opinion on therapeutic patents
|August 18, 2025
概括
小分子Traf2和Nck相互作用激酶 (TNIK) 抑制剂显示出有前途的结果,其中一种进展到治疗异常性肺纤维化症的临床试验. 由于途径的复杂性和类似药物的特性,瘤学应用仍然存在挑战.
科学领域:
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
- 分子生物学分子生物学
背景情况:
- 交互Traf2和Nck激酶 (TNIK) 是一个关键激酶,参与Wnt/β-catenin信号传递,细胞骨组织和免疫反应.
- TNIK在各种组织中表达,并与瘤学,神经疾病和纤维化有关.
- 针对TNIK的小分子抑制剂具有显著的治疗意义.
研究的目的:
- 审查从2008年到2024年在专利中披露的小分子TNIK抑制剂的最新进展.
- 分析开发用于各种疾病征兆的TNIK抑制剂的进展和挑战.
主要方法:
- 专利文献审查侧重于小分子TNIK抑制剂.
- 抑制剂支架的分析,临床试验的进展,以及进步或退缩的原因.
主要成果:
- 超过10项专利描述了多个TNIK抑制剂支架.
- 只有一个抑制剂,INS018_055,已经达到异常性肺纤维化临床试验.
- 由于TNIK在致癌途径和分子特异性质方面的作用,瘤学的发展受到阻碍.
结论:
- 尽管有许多专利化的支架,但TNIK抑制剂的临床转化仍然有限.
- 激酶选择性,物理化学性质和药理动力学对于推进TNIK抑制剂至关重要.
- 需要进一步的研究,以克服开发用于瘤学和其他疾病的TNIK抑制剂的挑战.
更多相关视频
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
9.2K
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
11.4K
相关概念视频
Inhibition of Cdk Activity
4.9K
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...
4.9K
M-Cdk Drives Transition Into Mitosis
5.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
Targeted Cancer Therapies
7.8K
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...
There are several types of targeted therapies against...
7.8K
MAPK Signaling Cascades
6.0K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.0K
NF-κB-dependent Signaling Pathway
7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.8K
Patch Clamp
5.7K
Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
5.7K
