通过二元药理进行脑受限的mTOR抑制
Ziyang Zhang1, Qiwen Fan2,3, Xujun Luo2,3
1Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, CA, USA.
Nature
|September 14, 2022
概括
研究人员开发了一种新的策略, 这种方法使用药物的组合来准特定的大脑途径,增强中枢神经系统疾病的治疗潜力.
科学领域:
- 药理学
- 神经科学
- 癌症学
背景情况:
- 药物对目标组织的作用导致不良反应,限制了治疗应用.
- 中枢神经系统疾病需要具有特定大脑活性的药物来提高安全性和有效性.
研究的目的:
- 开发一种方法来实现脑受限抑制酶标,特别是哺乳动物标的拉皮素 (mTOR).
- 为了减轻与mTOR抑制剂相关的全身副作用,同时保持治疗效果.
主要方法:
- 使用一种脑透的mTOR抑制剂 (RapaLink-1) 与一种脑透的FKBP12配体 (RapaBlock) 结合使用.
- 从现有的药物架构中设计出一种可通用的方法来制造细胞透的FKBP12依赖性激酶抑制剂.
- 设计的抑制剂对RapaBlock具有被证明的失活性.
主要成果:
- 这种药物组合成功地减轻了mTOR抑制剂的全身作用.
- 在质母细胞瘤异种移植模型中,RapaLink-1的疗效保持不变.
- 开发的抑制剂可以抑制大脑受限的激酶.
结论:
- 这种策略使药物在中枢神经系统内有针对性的作用,减少非目标不良事件.
- 这种方法为开发用于各种神经疾病和癌症的脑特异性激酶抑制剂提供了多功能平台.
更多相关视频
05:28A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction
Published on: August 27, 2019
16.6K
08:04Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
19.1K
相关概念视频
01:22PI3K/mTOR/AKT Signaling Pathway
3.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.9K
03:03mTOR Signaling and Cancer Progression
3.9K
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...
3.9K