在激酶抑制剂开发中利用人工智能和机器学习:进展,挑战和未来前景
Mohamed S Elgawish1,2, Aya M Almatary3, Sawsan A Zaitone4,5
1Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt mohamed_elgawish@pharm.suez.edu.eg +20643230741 +82109893 8184.
RSC medicinal chemistry
|September 8, 2025
概括
人工智能 (AI) 和机器学习 (ML) 正在通过解决目标识别和抵抗等挑战,彻底改变激酶抑制剂药物发现. 这些计算方法加速了下一代酶向治疗的发展.
科学领域:
- 生物化学和药理学 生物化学和药理学
- 计算生物学和生物信息学
- 药物发现和开发 药物发现和开发
背景情况:
- 蛋白激酶是关键的细胞信号调节器,与癌症和自身免疫性疾病有关.
- 像伊马替尼布这样的激酶抑制剂证明了治疗价值,但在开发选择性和强效药物方面仍然存在挑战.
- 保存的ATP结合部位,非目标效应,耐药性和患者的可变性使酶抑制剂的发展复杂化.
研究的目的:
- 审查人工智能和机器学习在设计,优化和改造激酶抑制剂中的变革性应用.
- 探索AI/ML方法如何解决酶向药物发现的关键障碍.
- 突出AI/ML在加速新激酶抑制剂开发方面的潜力.
主要方法:
- 审查AI/ML方法,包括深度学习,图形神经网络和生成模型.
- 在药物发现管道中分析AI/ML应用:目标识别,虚拟查,SAR建模,耐药性预测和临床试验设计.
- 检查展示AI优化的激酶抑制剂 (例如BTK,EGFR) 的案例研究.
主要成果:
- 人工智能/ML方法为诸如目标识别,虚拟查和预测耐药性等挑战提供了解决方案.
- 案例研究表明,人工智能在优化激酶抑制剂方面具有现实影响.
- 目前的局限性包括数据稀疏性,模型可解释性以及计算和实验结果之间的差距.
结论:
- 与药物化学的AI/ML整合有望加速和完善激酶抑制剂的开发.
- 新兴方向包括联合学习,个性化激酶抑制剂和支持人工智能的组合疗法.
- 人工智能/ML具有很大的潜力,可以推动下一代酶向治疗的发展.
相关概念视频
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.9K
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:
3.9K
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
02:50Combination 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
02:54Protein Kinases and Phosphatases
4.4K
4.4K
02:54Protein Kinases and Phosphatases
15.0K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.0K
01:22PI3K/mTOR/AKT Signaling Pathway
5.4K
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...
5.4K