抗体-联体提供共价抑制剂,阻断瘤性素
Aaron Petruzzella1,2, Marine Bruand1,2, Albert Santamaria-Martínez1,2
1Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Nature chemical biology
|May 29, 2024
概括
研究人员使用非天然抑制剂开发了抗体药物合物,以选择性地向和抑制囊类甲素,为癌症和其他副作用减少的疾病提供了有前途的治疗策略.
科学领域:
- 生物化学 生物化学
- 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:
- 氨酸甲素是关键的蛋白酶,涉及各种疾病,包括癌症.
- 目前的系统性抑制策略面临挑战,原因是异于目标效应和毒性.
- 需要有针对性的治疗方法来选择性地抑制 cathepsins.
研究的目的:
- 开发一种基于抗体的新型平台,用于针对性地提供非天然抑制剂 (NNPIs).
- 为氨酸甲素产生选择性抑制剂,具有潜在的治疗应用.
- 为了克服系统性蛋白酶抑制的局限性.
主要方法:
- 用反应性弹头进行共价抑制的NNPIs的功能化.
- 使用深度和突变发生的NNPIs的优化.
- 结合NNPIs与抗体进行细胞类型特定的输送.
- 在体外和体内对抗体-抑制剂结合物的评估.
主要成果:
- 开发的抗体-抑制剂结合物表明,它们在癌细胞和骨质细胞中特异性抑制了甲素活性.
- 结合物在体外和体外模型中都表现出显著的治疗疗效.
- 该平台可以快速设计和优化选择性蛋白酶抑制剂.
结论:
- 基于抗体的模块化平台促进了向药物递送,以抑制囊类甲素.
- 这种方法提供了一种策略,以减轻与系统性抑制相关的副作用.
- 该平台可用于开发针对癌症和其他疾病相关的各种蛋白酶的向抑制剂.
相关概念视频
02:57Targeted Cancer Therapies
7.5K
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...
7.5K
02:50Combination Therapies and Personalized Medicine
4.9K
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...
4.9K
01:27Tumor Immunotherapy
514
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
514
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.4K
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:
Major types that are helpful drug targets include:
2.4K