解锁大麻的反向准机制:揭示新的治疗途径
Wen Zeng1,2, Yifei Wang1, Rui Gao1
1School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
Journal of medicinal chemistry
|August 2, 2024
概括
大麻素 (CBD) 和 Δ9-四大麻素 (THC) 激活GPR18受体,影响细胞迁移. 这项研究揭示了CBD作为部分激动剂和THC作为完全激动剂,详细介绍了它们在分子水平上的独特激活机制.
科学领域:
- 分子药理学分子药理学
- 大麻素研究 研究 大麻素研究
- 细胞生物学 细胞生物学
背景情况:
- 大麻 (CBD) 和 Δ9-四大麻 (THC) 是具有显著生物活性的关键大麻sativa化合物.
- GPR18是一种参与各种生理过程的受体.
- 了解大麻素与GPR18的分子相互作用对于阐明它们的影响至关重要.
研究的目的:
- 确定CBD的分子标并阐明其作用机制.
- 为了比较CBD和THC在GPR18受体上的结合亲和力和激活机制.
- 研究GPR18在CBD诱导的子宫内膜上皮细胞迁移中的作用.
主要方法:
- 诱导适合对接 (IFD) 来预测结合亲和关系.
- 分子动力学 (MD) 模拟来分析复杂的稳定性和构造变化.
- 定向分子动力学 (SMD) 来评估对GPR18活性口袋的影响.
主要成果:
- GPR18被确定为CBD的点,激活p42/p44 MAPK通路并促进细胞迁移.
- THC对GPR18表现出比CBD更高的亲和力.
- CBD充当部分激动剂,诱导稳定构造,而THC充当全激动剂,在GPR18活性囊中产生"收缩空间"和机械约束.
结论:
- 该研究阐明了CBD和THC与GPR18相互作用的独特分子机制,区分了部分和完全的激动性.
- 这些发现提供了关于这些大麻素如何调节GPR18活性,影响细胞迁移的见解.
- 结合IFD-MD-SMD方法为研究GPR18激动剂的激活机制提供了有价值的方法.
更多相关视频
相关概念视频
Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
208
Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
Two synthetic agonists of THC,...
Two synthetic agonists of THC,...
208
Targets for Drug Action: Overview
6.1K
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...
6.1K
Drug Discovery: Overview
7.7K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.7K
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
172
CNS stimulants, such as cocaine, amphetamines, and cannabinoids, have varying structures and mechanisms of action that lead to different therapeutic effects and side effects. Cocaine, with its molecular formula C17H21NO4, is a tropane alkaloid and a tertiary amino compound. It has two chemical forms: the hydrochloride salt and the "freebase." The former is in powder form, while the latter involves removing the hydrochloride salt to create a form that can be smoked. Cocaine exerts its...
172
Targeted 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
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K


