针对代谢疾病的腺素受体的天然药物的计算发现
Peng Wang1, Zhiyu Xu1, Yuqing Deng1
1School of Electronic Information, Hunan First Normal University, Changsha, China.
Frontiers in pharmacology
|September 18, 2025
概括
这项研究使用人工智能发现了针对糖尿病等代谢疾病的腺受体的天然化合物. 人工智能框架设计了选择性,低毒性的候选药物,显示了植物医学创新的前景.
科学领域:
- 计算化学和药物发现
- 代谢性疾病研究研究.
- 腺受体的药理学 腺受体的药理学
背景情况:
- 代谢性疾病 (2型糖尿病,肥胖,NAFLD,癌症) 是全球性的健康挑战,具有共同的机制,如胰岛素抵抗.
- 目前对代谢性疾病的治疗方法是不理想的,这增加了对天然药物的兴趣.
- 氨酸受体 (ARs) 是葡萄糖代谢,脂质平衡和细胞应激的关键调节者,使它们成为治疗点.
研究的目的:
- 使用多式计算策略设计用于代谢疾病的自然药物候选物,以向腺受体 (AR).
- 通过同时准A1和A2AAR,并使用A2A选择性配体作为对照,探索亚型选择性.
- 通过结合低hERG通道亲和度过器来减轻潜在的毒性.
主要方法:
- 开发了一个集成QSAR,LSTM神经网络,强化学习和帕雷托优化的计算框架.
- 利用随机森林QSAR进行活动预测,并堆叠LSTM生成植物衍生分子.
- 采用进化操作 (交叉,突变,选择) 来增强分子多样性和性能.
主要成果:
- 成功生成了具有针对氨酸受体亚型 (A1和A2A) 高选择性的天然化合物.
- 设计的化合物表现出预测的低毒性 (hERG亲和力) 和良好的药物相似性.
- 产生的分子表现出有利的合成可访问性.
结论:
- 拟议的人工智能驱动框架为发现代谢疾病的天然药物提供了一个强大的战略.
- 突出结合植物医学与人工智能的潜力,以实现治疗创新.
- 证明了先进的计算方法在天然产品药物发现中的成功应用.
更多相关视频
11:29HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
Published on: July 20, 2016
11.5K
04:17Author Spotlight: Advancing Cellular and Protein Engineering to Control Biological Functions and Develop Novel Therapies
Published on: September 27, 2024
1.1K
相关概念视频
01:26Drug Discovery: Overview
11.1K
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...
11.1K
01:28Structure-Activity Relationships and Drug Design
1.7K
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.7K
01:25Adrenergic Agonists: Indirect-Acting Agents
2.6K
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
2.6K
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.8K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.8K
01:26Targets 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
01:30Adrenergic Agonists: Direct-Acting Agents
2.6K
Drugs that mimic the action of endogenous catecholamines like noradrenaline and adrenaline are called adrenergic agonists or sympathomimetics. Based on their mechanism of action, sympathomimetics can be classified as direct-, indirect-, or mixed-acting sympathomimetics. Direct-acting adrenergic agonists activate adrenoceptors without affecting presynaptic neurons, making them independent of neuronal catecholamine-depleting agents like reserpine and guanethidine.
These agents can be classified...
These agents can be classified...
2.6K