针对MDM2的PROTAC的概述,作为癌症治疗的新方法
Huiwen Li1, Xinhui Cai2, Xiaoyu Yang2
1Drug Discovery & Development Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
European journal of medicinal chemistry
|May 18, 2024
概括
用PROTAC技术准MDM2蛋白质提供了一种新的癌症治疗方法. 这种方法降解了MDM2,重新激活了p53通路,克服了对传统MDM2抑制剂的抗性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 在野生型TP53癌症中,MDM2基因放大/改变表达是常见的.
- 针对MDM2的p53结合口袋是一个有前途的治疗策略.
- 现有的MDM2抑制剂面临着药物耐药性和血液毒性等挑战.
研究的目的:
- 审查MDM2向降解的蛋白质溶解向嵌合体 (PROTAC) 分子.
- 探索PROTACs在癌症治疗中重新激活p53通路方面的潜力.
- 为MDM2蛋白和p53通路研究提供见解.
主要方法:
- 对代表性的MDM2 PROTAC降解剂的审查.
- 在药物发现和开发中分析PROTAC技术.
- 概述PROTACs的临床前和临床应用.
主要成果:
- PROTAC技术为MDM2有针对性的降解提供了一种新的方法.
- 通过PROTACs降解MDM2可以导致p53的重新激活.
- 在克服传统MDM2抑制剂的局限性方面,PROTACs显示出有前途.
结论:
- MDM2 PROTAC降解剂代表了癌症治疗的有前途的治疗策略.
- 通过PROTACs向蛋白质降解具有克服耐药性和毒性的潜力.
- 对MDM2 PROTACs的进一步研究可以促进针对p53通路的癌症治疗.
相关概念视频
Targeted Cancer Therapies
7.6K
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...
7.6K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
M-Cdk Drives Transition Into Mitosis
5.6K
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...
5.6K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Electron Transport Chain: Complex I and II
13.0K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.0K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K


