代谢,一个勃发展的小分子抗癌药物的目标
Michela Puxeddu1, Romano Silvestri1, Giuseppe La Regina1
1Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Molecules (Basel, Switzerland)
|September 13, 2025
概括
通过小分子抑制剂对关键代谢途径 (如糖解和谷氨酸代谢) 的重编程来准癌细胞的重编程,显示出开发具有降低毒性的有效抗癌剂的前景.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 药物发现 药物发现 药物发现
背景情况:
- 癌细胞表现出改变的新陈代谢,特别是增加了有氧糖解 (Warburg效应),推动了快速增殖.
- 重编程代谢途径是癌症治疗中公认的治疗目标.
研究的目的:
- 审查针对关键癌症代谢途径的小分子抑制剂的最新进展.
- 分析这些抑制剂对LDH,HK2,PKM2,GLS和FASN等酶的作用机制.
主要方法:
- 小分子抑制剂的文献综述.
- 在癌症中对代谢途径调节的分析.
- 酶特异性的向策略. 酶特异性的向策略.
主要成果:
- 针对糖解,谷氨胺代谢和脂肪酸合成的小分子抑制剂正在开发中.
- 这些抑制剂通过多种机制起作用,向参与癌症代谢的关键酶.
结论:
- 基于新陈代谢的策略对于开发下一代抗癌药物至关重要.
- 针对癌症代谢提供了提高疗效和减少全身毒性的潜力.
相关概念视频
Targeted Cancer Therapies
8.6K
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...
8.6K
Targets for Drug Action: Overview
10.1K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
10.1K
Combination Therapies and Personalized Medicine
5.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.9K
Electron Transport Chain: Complex I and II
18.5K
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...
18.5K
Adaptive Mechanisms in Cancer Cells
7.0K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.0K
Cancer
53.5K
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
53.5K


