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Operational and path dependencies impede the feasibility of hospital-based production of individually engineered drugs. 操作依赖性和路径依赖性阻碍了在医院生产个性化工程药物的可行性。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-17 DOI: 10.1016/j.drudis.2025.104434
Bora Zwart, Sandra Sülz, Jan Dekker, Maarten Ijzerman
{"title":"Operational and path dependencies impede the feasibility of hospital-based production of individually engineered drugs.","authors":"Bora Zwart, Sandra Sülz, Jan Dekker, Maarten Ijzerman","doi":"10.1016/j.drudis.2025.104434","DOIUrl":"10.1016/j.drudis.2025.104434","url":null,"abstract":"<p><p>Hospital-based production of gene therapies is a promising new approach for patients with high unmet medical needs, particularly those with rare diseases. However, operational and technical path dependencies (e.g. supply of materials, production timelines, and infrastructure limitations) and regulatory ambiguity impede hospitals from expediting implementation. We describe two distinct pathways including dependencies and uncertainty in manufacturing: complete in-house production and procurement of the active pharmaceutical ingredient. To realise the potential of hospital-based production at scale, future research should quantify infrastructure and staffing needs, analyse the alignment of production capabilities with patient demand, and scale up scenarios to improve delivery of therapies.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104434"},"PeriodicalIF":6.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666692","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
Corrigendum to "Targeting mutant EGFR in non-small cell lung cancer in the context of cell adaptation and resistance" [Drug Discov. Today 30(7) (2025) 104407]. “在细胞适应和耐药的背景下靶向非小细胞肺癌中的突变EGFR”[药物发现]的勘误表。今天30(7)(2025)104407]。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-17 DOI: 10.1016/j.drudis.2025.104426
Selene K Roberts, Ioannis Galgadas, David T Clarke, Laura C Zanetti-Domingues, Francesco L Gervasio, Marisa L Martin-Fernandez
{"title":"Corrigendum to \"Targeting mutant EGFR in non-small cell lung cancer in the context of cell adaptation and resistance\" [Drug Discov. Today 30(7) (2025) 104407].","authors":"Selene K Roberts, Ioannis Galgadas, David T Clarke, Laura C Zanetti-Domingues, Francesco L Gervasio, Marisa L Martin-Fernandez","doi":"10.1016/j.drudis.2025.104426","DOIUrl":"10.1016/j.drudis.2025.104426","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104426"},"PeriodicalIF":6.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635822","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
Innovation testbeds as enabling ecosystems driving nanopharmaceuticals to market 创新试验台，使生态系统推动纳米药物推向市场。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-15 DOI: 10.1016/j.drudis.2025.104433
Luis Padrela , Rabah Mouras , Donal Killackey
{"title":"Innovation testbeds as enabling ecosystems driving nanopharmaceuticals to market","authors":"Luis Padrela ,&nbsp;Rabah Mouras ,&nbsp;Donal Killackey","doi":"10.1016/j.drudis.2025.104433","DOIUrl":"10.1016/j.drudis.2025.104433","url":null,"abstract":"<div><div>It is a major challenge to produce proof-of-concept (PoC) pharmaceutical nanoformulations of the required quality level, and in sufficient quantities for late preclinical and clinical testing. The creation of bespoke capabilities to assist in the translation of early stage PoC medicines could greatly reduce time and cost to bring new and innovative therapies to the market. This paper reflects on current barriers hampering the commercialization of novel nanopharmaceuticals and discusses the potential for integrated approaches to bring together existing and new processing infrastructures to de-risk and accelerate the development, manufacturing and market entry of the next-generation nanopharmaceuticals.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104433"},"PeriodicalIF":6.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657996","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
Unlocking new frontiers in kidney diseases: targeting endothelial dysfunction with emerging biomarkers and therapies 打开肾脏疾病的新领域：用新兴的生物标志物和疗法靶向内皮功能障碍。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-14 DOI: 10.1016/j.drudis.2025.104432
Rohan Bhadange, Anil Bhanudas Gaikwad
{"title":"Unlocking new frontiers in kidney diseases: targeting endothelial dysfunction with emerging biomarkers and therapies","authors":"Rohan Bhadange,&nbsp;Anil Bhanudas Gaikwad","doi":"10.1016/j.drudis.2025.104432","DOIUrl":"10.1016/j.drudis.2025.104432","url":null,"abstract":"<div><div>Kidney diseases are a global health concern with increasing morbidity and mortality. Their progression involves multiple pathological mechanisms, including inflammation, oxidative stress, apoptosis, glomerulosclerosis, fibrosis, renin–angiotensin–aldosterone system (RAAS) activation, and endothelial dysfunction. The endothelin (ET) system has a key role in vascular homeostasis, and its dysfunction is linked to kidney diseases. However, few endothelial dysfunction biomarkers and therapeutic targets have been identified. In this review, we explore emerging biomarkers, such as endoglin, periostin, fetuin-A, endocan, cytokeratin (CK)-18, and others, highlighting their diagnostic and therapeutic potential. Identifying these biomarkers could advance novel therapeutic strategies for effective kidney disease management in preclinical and clinical settings.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104432"},"PeriodicalIF":6.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648122","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
Comparative study of innovative computational methods for identifying cryptic pockets 识别隐口袋的创新计算方法的比较研究。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-11 DOI: 10.1016/j.drudis.2025.104430
Yonggui Li , Lingling Song , Yawen Dong , Ge-Fei Hao
{"title":"Comparative study of innovative computational methods for identifying cryptic pockets","authors":"Yonggui Li ,&nbsp;Lingling Song ,&nbsp;Yawen Dong ,&nbsp;Ge-Fei Hao","doi":"10.1016/j.drudis.2025.104430","DOIUrl":"10.1016/j.drudis.2025.104430","url":null,"abstract":"<div><div>Cryptic pockets are crucial targets in drug discovery, yet their transient and concealed nature makes experimental detection challenging. Computational methods have proven highly effective for identifying and characterizing these elusive sites. Here, we systematically summarize and analyze state-of-the-art computational methods for cryptic pocket detection. Specifically, we examine their nature, mechanisms of formation, and functions, and review computational methods for cryptic pocket detection. To illustrate their practical utility, we present a case study of TEM-1 β-lactamase. This review aims to guide researchers in harnessing these computational tools to uncover cryptic pockets and promote their application in drug discovery.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104430"},"PeriodicalIF":6.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625143","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
Advantages, progress, and future trends in oral medicated jellies/gels: Focus on adherence aspects 口服给药果冻/凝胶的优势、进展和未来趋势：关注粘附性方面。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-11 DOI: 10.1016/j.drudis.2025.104431
Xinyue Huang , Yingying Mu , Lan Shen , Lijie Zhao
{"title":"Advantages, progress, and future trends in oral medicated jellies/gels: Focus on adherence aspects","authors":"Xinyue Huang ,&nbsp;Yingying Mu ,&nbsp;Lan Shen ,&nbsp;Lijie Zhao","doi":"10.1016/j.drudis.2025.104431","DOIUrl":"10.1016/j.drudis.2025.104431","url":null,"abstract":"<div><div>Poor medication adherence is a pervasive issue in oral administration. Oral medicated jellies/gels are semisolid formulations that leverage the advantages of both solid and liquid formulations and have a promising potential. They help to increase patient comfort, simplify the medication process, and improve the medication experience, thereby improving medication adherence and alleviating many common barriers to adherence. This review analyzes the advantages of oral jellies from the perspective of improving adherence and summarizes the current state of research on this dosage form at five levels: improved bioavailability, drug release, swallowability, palatability, and appearance appeal. Finally, we discuss future research directions for this formulation.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104431"},"PeriodicalIF":6.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625142","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
Dynamic chromatin accessibility landscape changes in cardiac fibrosis 心肌纤维化中染色质可及性动态变化。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-08 DOI: 10.1016/j.drudis.2025.104429
Zhen-Yu Liu , Peng Liu , Li-Chan Lin , Jing-Jing Yang , Hui Tao
{"title":"Dynamic chromatin accessibility landscape changes in cardiac fibrosis","authors":"Zhen-Yu Liu ,&nbsp;Peng Liu ,&nbsp;Li-Chan Lin ,&nbsp;Jing-Jing Yang ,&nbsp;Hui Tao","doi":"10.1016/j.drudis.2025.104429","DOIUrl":"10.1016/j.drudis.2025.104429","url":null,"abstract":"<div><div>Cardiac fibrosis is characterized by the activation and abnormal proliferation of cardiac fibroblasts into myofibroblasts, which secrete excessive amounts of extracellular matrix proteins. Dynamic changes in chromatin accessibility regulate the structural accessibility of chromatin DNA during transcription and replication. Chromatin accessibility influences gene expression by modulating the interactions between <em>cis</em>-regulatory elements and <em>trans</em>-acting factors. Under pathological conditions, alterations in chromatin accessibility lead to changes in the expression of fibrosis-related genes, thereby contributing to the onset and progression of cardiac fibrosis. In this review, we summarize current methods for measuring chromatin accessibility and examine the roles of chromatin dynamics and transcription factors in the regulation of cardiac fibrosis.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104429"},"PeriodicalIF":6.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606990","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
Cold atmospheric plasma in drug delivery and skin treatment 低温大气等离子体在给药和皮肤治疗中的应用。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-08 DOI: 10.1016/j.drudis.2025.104428
Jing Chen , Jingru Zhao , Jing Liu , Xiaoqing Miao
{"title":"Cold atmospheric plasma in drug delivery and skin treatment","authors":"Jing Chen ,&nbsp;Jingru Zhao ,&nbsp;Jing Liu ,&nbsp;Xiaoqing Miao","doi":"10.1016/j.drudis.2025.104428","DOIUrl":"10.1016/j.drudis.2025.104428","url":null,"abstract":"<div><div>This is a review of the application of an emerging technology in drug delivery and skin treatment – cold atmospheric pressure plasma (CAP). It can be used to modify the polymer surface by introducing functional groups that enhance hydrophilicity and biocompatibility, improve skin permeability through fatty acid oxidation and electroporation, and enhance the antibacterial ability of antibiotics, and it can be synergistically delivered with nanoparticles to regulate cytokines and growth factors, reduce inflammation, and promote cell proliferation, thereby facilitating local drug delivery, wound healing, and the treatment of skin diseases. CAP is a multipurpose technology that offers great potential for personalized medicine and advanced therapeutic applications. Further research is needed to optimize treatment plans and understand the underlying mechanisms.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104428"},"PeriodicalIF":6.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606966","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 PBPK/PD modeling in drug discovery: A CRO perspective 药物发现中的翻译PBPK/PD建模：一个CRO视角。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-08 DOI: 10.1016/j.drudis.2025.104427
Simone Esposito, David Cebrián
{"title":"Translational PBPK/PD modeling in drug discovery: A CRO perspective","authors":"Simone Esposito,&nbsp;David Cebrián","doi":"10.1016/j.drudis.2025.104427","DOIUrl":"10.1016/j.drudis.2025.104427","url":null,"abstract":"<div><div>The use of translational physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling has become a standard practice in drug discovery, providing advanced data integration accounting for species-specific physiology and target pharmacology. This paper provides a preclinical contract research organization (CRO) perspective on the applications, benefits, and challenges of translational PBPK/PD modeling approaches in integrated drug discovery (IDD) collaborations. We also describe how PBPK/PD approaches have impacted the role of the drug metabolism and pharmacokinetics project representative (DPR) within CROs. We propose that adopting translational PBPK/PD approaches enhances the sponsor–CRO IDD partnership by fostering data-driven project decision-making and optimizing the use of resources.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 8","pages":"Article 104427"},"PeriodicalIF":6.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606991","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
Advancements and challenges in using AI for biomarker detection in early Alzheimer’s disease 人工智能用于早期阿尔茨海默病生物标志物检测的进展和挑战。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-07-01 DOI: 10.1016/j.drudis.2025.104415
Iman Beheshti , Benedict C. Albensi , Alex Freitas , Taravat Ghafourian
{"title":"Advancements and challenges in using AI for biomarker detection in early Alzheimer’s disease","authors":"Iman Beheshti ,&nbsp;Benedict C. Albensi ,&nbsp;Alex Freitas ,&nbsp;Taravat Ghafourian","doi":"10.1016/j.drudis.2025.104415","DOIUrl":"10.1016/j.drudis.2025.104415","url":null,"abstract":"<div><div>The rapid growth in Alzheimer’s disease (AD) research has led to an unprecedented accumulation of biomedical and clinical data, including longitudinal patient datasets and comprehensive observational cohort databases comprising clinical, biomedical, neuroimaging and lifestyle data. Expert use of machine learning algorithms is indispensable in order to realize the full potential of the data for diagnosis and drug target discovery. Here, we provide an overview of the biomedical and neuroimaging measures for AD diagnosis and staging. We then critically review the application of machine learning (classification) methods to AD data and provide insight for future improvements and research directions. Future research should aim to improve interpretability, accessibility and thorough validation of the models, enabling translation into clinical applications.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104415"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367757","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
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