发布求助
文献互助 智能选刊 最新文献

Drug Discovery Today最新文献

筛选
英文 中文
Unraveling the potential of diffusion models in small-molecule generation 揭示扩散模型在小分子生成中的潜力。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104413
Peining Zhang , Daniel Baker , Minghu Song , Jinbo Bi
{"title":"Unraveling the potential of diffusion models in small-molecule generation","authors":"Peining Zhang ,&nbsp;Daniel Baker ,&nbsp;Minghu Song ,&nbsp;Jinbo Bi","doi":"10.1016/j.drudis.2025.104413","DOIUrl":"10.1016/j.drudis.2025.104413","url":null,"abstract":"<div><div>Generative artificial intelligence (AI) presents chemists with novel ideas for drug design and facilitates the exploration of vast chemical spaces. As an emerging tool, diffusion models (DMs) have recently attracted great attention in drug research and development (R&amp;D). Here, we comprehensively review the latest advances in, and applications of, DMs in molecular generation. We introduce the theoretical principles of DMs and then categorize various DM-based molecular generation methods according to their mathematical and chemical applications. We also examine the performance of these models on benchmark datasets, with a particular focus on comparing the generation performance of existing 3D methods. Finally, we conclude by emphasizing current challenges and suggesting future research directions to fully exploit the potential of DMs in drug discovery.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104413"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antimicrobial Resistance: From Ukraine to Gaza 抗生素耐药性：从乌克兰到加沙。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104411
Santanu Datta
{"title":"Antimicrobial Resistance: From Ukraine to Gaza","authors":"Santanu Datta","doi":"10.1016/j.drudis.2025.104411","DOIUrl":"10.1016/j.drudis.2025.104411","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104411"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting mutant EGFR in non-small cell lung cancer in the context of cell adaptation and resistance 靶向EGFR突变体在非小细胞肺癌中的细胞适应性和耐药性研究
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104407
Selene K. Roberts , Ioannis Galgadas , David T. Clarke , Laura C. Zanetti-Domingues , Francesco L. Gervasio , Marisa L. Martin-Fernandez
{"title":"Targeting mutant EGFR in non-small cell lung cancer in the context of cell adaptation and resistance","authors":"Selene K. Roberts ,&nbsp;Ioannis Galgadas ,&nbsp;David T. Clarke ,&nbsp;Laura C. Zanetti-Domingues ,&nbsp;Francesco L. Gervasio ,&nbsp;Marisa L. Martin-Fernandez","doi":"10.1016/j.drudis.2025.104407","DOIUrl":"10.1016/j.drudis.2025.104407","url":null,"abstract":"<div><div>Activating mutations in the catalytic kinase domain of the epidermal growth factor receptor (EGFR) are crucial drivers of non-small cell lung cancer (NSCLC). Our understanding of the structural changes induced by such mutations has evolved alongside the rational design of targeted tyrosine kinase inhibitors (TKIs), leading to improved anti-tumor responses through appropriate patient stratification. However, challenges remain, including a growing number of therapy adaptation mechanisms and acquired resistance, which are further complicated by the intricate signaling networks of EGFR. Here, we review the rational development and targeting of EGFR-TKIs in the context of TKI-induced cellular death, adaptation, resistance, and eventual clinical failure, to provide a birds-eye view of this highly multidisciplinary field. We end by proposing new approaches based on our developing understanding of the quaternary structure of EGFR, which leverage <em>in situ</em> oligomer architectures to develop therapies that modulate EGFR oligomer-specific interactions and exploit weaknesses in its downstream signaling network to overcome resistance.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104407"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Translational PK/PD: a retrospective analysis of performance and impact from a drug portfolio 翻译PK/PD：从药物组合的性能和影响的回顾性分析。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104417
Rasmus Jansson-Löfmark , Markus Fridén , Lassina Badolo , Christine Ahlström , Ian Gurrell , Menelas N. Pangalos , Rhys DO Jones
{"title":"Translational PK/PD: a retrospective analysis of performance and impact from a drug portfolio","authors":"Rasmus Jansson-Löfmark ,&nbsp;Markus Fridén ,&nbsp;Lassina Badolo ,&nbsp;Christine Ahlström ,&nbsp;Ian Gurrell ,&nbsp;Menelas N. Pangalos ,&nbsp;Rhys DO Jones","doi":"10.1016/j.drudis.2025.104417","DOIUrl":"10.1016/j.drudis.2025.104417","url":null,"abstract":"<div><div>Attrition in drug development continues to be dominated by failure in clinical mid-stage proof-of-concept studies. Successfully demonstrating proof-of-mechanism (PoM) has been reported to be a key factor to improve clinical success. Accurate prediction and testing of PoM are crucial. This analysis of AstraZeneca’s portfolio assesses the role of translational PK/PD modelling in predicting clinical PoM. It has found that 83% of compounds had drug exposure–response within a threefold prediction accuracy. Notably, projects with robust PK/PD packages achieved an 85% success rate in PoM, compared with 33% for those with basic packages. This highlights how translational PK/PD modelling can significantly enhance success rates for drugs entering clinical trials.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104417"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring nucleotide and non-nucleotide cGAS-STING agonists: Therapeutic applications and future directions in cancer immunotherapy 探索核苷酸和非核苷酸cGAS-STING激动剂：在癌症免疫治疗中的治疗应用和未来方向。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104412
Abhishek Ghara , Gurubasavaraja Swamy Purawarga Matada , Payel Pramanick , Uday Raj Sharma , Prasad Sanjay Dhiwar
{"title":"Exploring nucleotide and non-nucleotide cGAS-STING agonists: Therapeutic applications and future directions in cancer immunotherapy","authors":"Abhishek Ghara ,&nbsp;Gurubasavaraja Swamy Purawarga Matada ,&nbsp;Payel Pramanick ,&nbsp;Uday Raj Sharma ,&nbsp;Prasad Sanjay Dhiwar","doi":"10.1016/j.drudis.2025.104412","DOIUrl":"10.1016/j.drudis.2025.104412","url":null,"abstract":"<div><div>The STING (stimulator of interferon genes) pathway plays a crucial role in immune defense against carcinoma. This review highlights its role in antigen response, tumor infiltration, and T-cell activation. Despite the promise of STING agonists, challenges like drug stability and toxicity hinder clinical success. Nanoparticle-based drug delivery and combinatorial strategies offer potential solutions to enhance efficacy and minimize resistance. Ongoing research focuses on developing novel STING agonists for improved cancer treatment. This article explores the pathway’s immunological significance, biochemical mechanisms, and pharmacological hurdles while discussing strategies to enhance the potency, safety, and therapeutic potential of STING-targeted therapies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104412"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Collaborative innovation during the drug discovery and development process 药物发现和开发过程中的协同创新。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104409
Xue Wu , Mirjam Knockaert , Paolo Blasi
{"title":"Collaborative innovation during the drug discovery and development process","authors":"Xue Wu ,&nbsp;Mirjam Knockaert ,&nbsp;Paolo Blasi","doi":"10.1016/j.drudis.2025.104409","DOIUrl":"10.1016/j.drudis.2025.104409","url":null,"abstract":"<div><div>Given the complexity and resource-intensive nature of the drug discovery and development process, breakthrough innovations often stem from multidisciplinary collaborations. This systematic literature review examines collaborative innovation within this process, analyzing current practices and identifying future research directions. The review used an evidence-based approach, retrieving 737 papers through a Web of Science “All Databases” search, and ultimately selecting 74 articles for discussion. The articles were categorized according to the initiation, implementation, and closure phases of collaborative innovation, and were classified into homogeneous and heterogeneous collaborations. Using this framework, we systematically reviewed the existing knowledge, with a particular focus on how collaborative innovation can be successfully initiated and implemented, and how it can generate positive outcomes for drug research.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104409"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A step closer to medicinal product harmonisation: EMA PMS becomes the next focus of IDMP efforts 离药品统一又近了一步：EMA PMS成为IDMP工作的下一个重点。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104410
Michiel Stam
{"title":"A step closer to medicinal product harmonisation: EMA PMS becomes the next focus of IDMP efforts","authors":"Michiel Stam","doi":"10.1016/j.drudis.2025.104410","DOIUrl":"10.1016/j.drudis.2025.104410","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104410"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computational approaches to DMPK: A realistic assessment of current methods and their practical impact. Part I: Physicochemical and in vitro properties DMPK的计算方法：对当前方法及其实际影响的现实评估。第一部分：理化和体外特性。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-06-30 DOI: 10.1016/j.drudis.2025.104422
Koichi Handa , Mariko Hirano , Michiharu Kageyama , Andreas Bender
{"title":"Computational approaches to DMPK: A realistic assessment of current methods and their practical impact. Part I: Physicochemical and in vitro properties","authors":"Koichi Handa ,&nbsp;Mariko Hirano ,&nbsp;Michiharu Kageyama ,&nbsp;Andreas Bender","doi":"10.1016/j.drudis.2025.104422","DOIUrl":"10.1016/j.drudis.2025.104422","url":null,"abstract":"<div><div>Artificial intelligence and computational approaches have received considerable interest in recent years, and here we assess their real-world utility in drug discovery projects. We review recent <em>in silico</em> models in the area of drug metabolism and pharmacokinetics (DMPK), especially for physicochemical properties (pKa and logD) and <em>in vitro</em> assays [solubility (DMSO, Dried-DMSO, Powder), permeability (PAMPA, Caco-2, MDCK), metabolic stability (liver microsome, hepatocyte), and protein binding (plasma, microsome, brain)]. We discuss which are currently fit for purpose (and which are not), bridging both computational and experimental aspects in the early drug discovery stages. The review includes diverse aspects of obtaining data and model generation, as well as modeler/experimentalist interplay.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104422"},"PeriodicalIF":6.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Back to gene therapy: bringing the EU regulation into the future 回到基因治疗：将欧盟监管带入未来。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-06-30 DOI: 10.1016/j.drudis.2025.104424
Umberto M. Musazzi , Paolo Rocco , Sara Manellari , Sara Azari , Giulio Pompilio , Paola Minghetti
{"title":"Back to gene therapy: bringing the EU regulation into the future","authors":"Umberto M. Musazzi ,&nbsp;Paolo Rocco ,&nbsp;Sara Manellari ,&nbsp;Sara Azari ,&nbsp;Giulio Pompilio ,&nbsp;Paola Minghetti","doi":"10.1016/j.drudis.2025.104424","DOIUrl":"10.1016/j.drudis.2025.104424","url":null,"abstract":"<div><div>The current European framework for Advanced Therapy Medicinal Products (ATMPs), which also covers gene therapies, was established in 2007 at the dawn of the biotechnology era in the pharmaceutical sector. However, its inherent limitations have been revealed by the new frontiers enabled by the scientific and technological advances of the past few decades, particularly in the areas of innovative gene therapeutics (e.g., CRISPR/Cas9–RNA complexes), manufacturing technologies, and delivery systems. Here, we contribute to the scientific discussion on how to reduce regulatory uncertainty in the qualification of medicinal products with a different mechanism of action (e.g., editing the host genome or regulating gene expression), and on rationalizing regulatory support and incentives for the most complex therapies in terms of mechanism of action and manufacturing process.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104424"},"PeriodicalIF":6.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lysine lactylation: Regulatory mechanisms, role in health and disease, and its therapeutic potential 赖氨酸乳酸化：调节机制，在健康和疾病中的作用，及其治疗潜力。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-06-30 DOI: 10.1016/j.drudis.2025.104420
Xu Yan , Guangming Zhang , Huayuan Wei , Lin Yang , Xijuan Jiang
{"title":"Lysine lactylation: Regulatory mechanisms, role in health and disease, and its therapeutic potential","authors":"Xu Yan ,&nbsp;Guangming Zhang ,&nbsp;Huayuan Wei ,&nbsp;Lin Yang ,&nbsp;Xijuan Jiang","doi":"10.1016/j.drudis.2025.104420","DOIUrl":"10.1016/j.drudis.2025.104420","url":null,"abstract":"<div><div>Lysine lactylation of (Kla), a novel post-translational modification, is prevalent in various diseases and has garnered increasing attention. Kla has diverse roles in diseases, exhibiting both beneficial and detrimental effects depending on the context and modification site. This review focuses on the emerging therapeutic potential of Kla in various diseases. We discuss recent studies that have underscored the therapeutic potential of Kla and its inhibitors in treating diverse disorders. We also explore potential therapeutic strategies targeting Kla and its substrates, providing a scientific basis and roadmap for subsequent research and drug development.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104420"},"PeriodicalIF":6.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
首页 上一页 下一页 尾页
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们：info@booksci.cn Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号：604180095
Book学术官方微信