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The R&D productivity challenge: transforming the pharmaceutical ecosystem. 研发生产力的挑战：改变制药生态系统。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-07 DOI: 10.1016/j.drudis.2025.104494
Alexander Schuhmacher, Oliver Gassmann, Sebastian Kwisda, Malte Kremer, Markus Hinder, Dominik Hartl
{"title":"The R&D productivity challenge: transforming the pharmaceutical ecosystem.","authors":"Alexander Schuhmacher, Oliver Gassmann, Sebastian Kwisda, Malte Kremer, Markus Hinder, Dominik Hartl","doi":"10.1016/j.drudis.2025.104494","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104494","url":null,"abstract":"<p><p>The persistent decline in pharmaceutical R&D productivity has been extensively analyzed and debated for over two decades, with profound implications for the structure and strategy of the pharmaceutical industry. This systemic challenge forced many leading companies to adapt their R&D models, influencing internal capabilities and external innovation strategies. In response, the industry has evolved into a complex, interdependent biopharmaceutical ecosystem encompassing large pharmaceutical corporations, biotech innovators and specialized service providers. Although R&D productivity affects all research-driven companies, its consequences are particularly pronounced for large pharmaceutical firms, because the scale and capital intensity of their R&D activities make productivity a crucial determinant of long-term competitiveness and sustainability. By contrast, other stakeholders are only partially adversely affected, whereas some can even obtain value from it.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104494"},"PeriodicalIF":7.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256995","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
Therapeutic strategies targeting ocular vasculopathies: Current advances and emerging challenges. 针对眼部血管病变的治疗策略：当前进展和新出现的挑战。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-07 DOI: 10.1016/j.drudis.2025.104496
Julie Le Du, Cyril Ronco
{"title":"Therapeutic strategies targeting ocular vasculopathies: Current advances and emerging challenges.","authors":"Julie Le Du, Cyril Ronco","doi":"10.1016/j.drudis.2025.104496","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104496","url":null,"abstract":"<p><p>Ocular vasculopathies, including neovascular age-related macular degeneration (wet AMD), diabetic retinopathy, retinal vein occlusion, and radiation maculopathy, are major causes of vision loss driven by vascular endothelial growth factor (VEGF)-mediated neovascularization. Anti-VEGF therapies have transformed outcomes but face limitations from resistance, variable response, frequent injections, and adverse effects of broad VEGF blockade. This review discusses emerging approaches, including platelet-derived growth factor (PDGF), angiopoietin-2 (Ang-2), tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2), and integrin inhibitors, alongside innovations in long-acting biologics, gene therapy, and nanocarriers. Complementary strategies targeting alternative angiogenic pathways, inflammation, hypoxia, and neuroprotection might overcome resistance and preserve retinal function. Together, these advances highlight opportunities to optimize therapy and address unmet needs in ocular vasculopathies.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104496"},"PeriodicalIF":7.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257021","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
Structure-guided approaches to modulate endosomal Toll-like receptors TLR7, TLR8 and TLR9: advances, challenges and therapeutic promise. 结构导向方法调节内体toll样受体TLR7、TLR8和TLR9：进展、挑战和治疗前景
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-07 DOI: 10.1016/j.drudis.2025.104495
Troy Matziol, Valerij Talagayev, Günther Weindl, Gerhard Wolber
{"title":"Structure-guided approaches to modulate endosomal Toll-like receptors TLR7, TLR8 and TLR9: advances, challenges and therapeutic promise.","authors":"Troy Matziol, Valerij Talagayev, Günther Weindl, Gerhard Wolber","doi":"10.1016/j.drudis.2025.104495","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104495","url":null,"abstract":"<p><p>TLR7, TLR8 and TLR9 are endosomal immune receptors central to antiviral defense, autoimmunity and cancer immunotherapy. Recent structural insights have revealed distinct ligand-binding mechanisms and conformational dynamics, enabling the design of selective small-molecule agonists and antagonists. This review summarizes key advances in TLR7/8/9 biology, pharmacology and structure-guided drug discovery. We highlight clinical progress, delivery strategies and translational challenges including species-specific differences and immune-related toxicities. Novel approaches such as nanoparticle systems and endogenous RNA mimetics promise targeted modulation of TLR activity. Together, these developments emphasize the therapeutic potential of precision TLR modulation in immunologically complex diseases.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104495"},"PeriodicalIF":7.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257069","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
Skin cancer chemoprevention: An overview. 皮肤癌化学预防：综述。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-07 DOI: 10.1016/j.drudis.2025.104493
Mariana Bastos, Lucília Saraiva, Ana Camila Marques, Maria Helena Amaral
{"title":"Skin cancer chemoprevention: An overview.","authors":"Mariana Bastos, Lucília Saraiva, Ana Camila Marques, Maria Helena Amaral","doi":"10.1016/j.drudis.2025.104493","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104493","url":null,"abstract":"<p><p>The incidence of melanoma and non-melanoma skin cancers (NMSCs) is rising worldwide, with ultraviolet radiation as a primary cause. Although NMSCs are more common, melanoma remains the most challenging to treat because of its higher aggressiveness, late diagnosis, and recurrence after therapy. Sunscreens provide limited protection, highlighting the need for alternative solutions. Chemopreventive therapies targeting molecular pathways involved in melanoma progression have shown promise. Certain synthetic and natural nontoxic compounds can inhibit skin carcinogenesis during the initiation, promotion, and progression stages. This review discusses the effects of chemopreventive agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), statins, antioxidants, and vitamins, on skin cancer. Although substantial preclinical evidence suggests these strategies might prevent or delay melanoma, clinical studies confirming efficacy and long-term safety are still lacking.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104493"},"PeriodicalIF":7.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256997","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
Bridging data and drug development: Machine learning approaches for next-generation ADMET prediction. 桥接数据和药物开发：下一代ADMET预测的机器学习方法。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-04 DOI: 10.1016/j.drudis.2025.104487
Nini Fan, Jing Chen, Jinghui Wang, Zhe-Sheng Chen, Yinfeng Yang
{"title":"Bridging data and drug development: Machine learning approaches for next-generation ADMET prediction.","authors":"Nini Fan, Jing Chen, Jinghui Wang, Zhe-Sheng Chen, Yinfeng Yang","doi":"10.1016/j.drudis.2025.104487","DOIUrl":"10.1016/j.drudis.2025.104487","url":null,"abstract":"<p><p>Absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation is fundamental to determining drug candidate clinical success. Traditional experimental methods, although reliable, are resource-intensive, whereas conventional computational models lack robustness and generalizability. Recent machine learning (ML) advances have transformed ADMET prediction by deciphering complex structure-property relationships, providing scalable, efficient alternatives. In this paper, we systematically examine state-of-the-art methodologies, including graph neural networks, ensemble learning, and multitask frameworks, as well as emerging strategies for multimodal data integration and algorithmic optimization aimed at enhancing predictive accuracy and translational relevance. By mitigating late-stage attrition, supporting preclinical decision-making, and expediting the development of safer and more efficacious therapeutics, ML-driven ADMET prediction exemplifies the transformative role of artificial intelligence in reshaping modern drug discovery and development.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104487"},"PeriodicalIF":7.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237472","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
Harnessing cold atmospheric plasma for skin cancer: a non-invasive breakthrough in plasma medicine. 利用低温大气等离子体治疗皮肤癌：等离子医学的非侵入性突破。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-03 DOI: 10.1016/j.drudis.2025.104491
Vaibhavi Meghraj Desai, Souradeep Dutta, Kaustubh Saoji, Priti Pal, Ram Prakash Lamba, Udit Narayan Pal, Aniruddha Roy, Gautam Singhvi
{"title":"Harnessing cold atmospheric plasma for skin cancer: a non-invasive breakthrough in plasma medicine.","authors":"Vaibhavi Meghraj Desai, Souradeep Dutta, Kaustubh Saoji, Priti Pal, Ram Prakash Lamba, Udit Narayan Pal, Aniruddha Roy, Gautam Singhvi","doi":"10.1016/j.drudis.2025.104491","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104491","url":null,"abstract":"<p><p>Skin cancer, including melanoma and non-melanoma, is a major global health concern as a result of rapid metastasis and recurrence. Key causes include ultraviolet (UV) radiation, aging, and genetic predisposition. Current treatments face challenges such as drug resistance, side effects, and relapse, prompting interest in novel therapies. Cold atmospheric plasma (CAP) is a promising alternative, producing reactive oxygen (ROS) and nitrogen species (RNS) that trigger oxidative stress-induced cell death of cancer cells. CAP also regulates signaling pathways linked to proliferation, apoptosis, and immunity, induces immunogenic cell death, and modulates calcium signaling. Preclinical and clinical studies revealed enhanced efficacy for its application in combination with chemotherapy and photodynamic therapy. In this review, we examine the mechanisms of action, combination strategies, clinical applications of CAP, as well as its potential in skin cancer treatment.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104491"},"PeriodicalIF":7.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231031","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
Optimizing innovation in pharma: how organizational agility unlocks quality performance through employee engagement. 优化制药创新：组织敏捷性如何通过员工敬业度解锁质量绩效。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104490
Nicholas M Rosemarino, Charles H Jones, Catarina R Dolsten
{"title":"Optimizing innovation in pharma: how organizational agility unlocks quality performance through employee engagement.","authors":"Nicholas M Rosemarino, Charles H Jones, Catarina R Dolsten","doi":"10.1016/j.drudis.2025.104490","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104490","url":null,"abstract":"<p><p>Pharmaceutical firms must balance innovation with rigorous quality standards. Drawing from Job Demands-Resources (JD-R) theory, we examined how organizational agility unlocks the benefits of an innovation-supportive climate. Using a two-wave methodological design from 250 employees in the USA, moderated mediation analyses demonstrated that innovation climate exerted indirect effects on quality performance through engagement, but only when organizational agility was high. These findings suggest that innovation climates alone are insufficient. Instead, organizational agility functions as the crucial organizational-level resource that channels creative energy into employee engagement and quality outcomes, a dynamic particularly salient in pharmaceutical settings.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104490"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224762","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
Improving B-cell epitope prediction. 改善b细胞表位预测。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104489
Hao Yu, Diane Joseph-McCarthy, Sandor Vajda
{"title":"Improving B-cell epitope prediction.","authors":"Hao Yu, Diane Joseph-McCarthy, Sandor Vajda","doi":"10.1016/j.drudis.2025.104489","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104489","url":null,"abstract":"<p><p>The prediction of antibody binding residues of an antigen is essential for understanding the immune response mechanisms and advancing antibody therapeutics. By definition, each epitope is the binding site of a specific antibody; however, many prediction methods are antibody-agnostic, and thus need only the structure of the antigen. Antibody-specific methods also require either the structure or models of the antibody, and are generally based on docking or co-folding algorithms. Machine learning methods have been improved substantially during the last few years, resulting in new approaches to epitope prediction. We evaluate some popular methods and show that combining AlphaFold 3 with the epitope prediction program AbEMap yields substantially better results than any of the other methods tested.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104489"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224743","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
The Role of Data Monitoring Committees in drug research 数据监测委员会在药物研究中的作用。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104474
Markus Hinder , Nandhini Madesh , Dominik Hartl , Alexander Schuhmacher
{"title":"The Role of Data Monitoring Committees in drug research","authors":"Markus Hinder ,&nbsp;Nandhini Madesh ,&nbsp;Dominik Hartl ,&nbsp;Alexander Schuhmacher","doi":"10.1016/j.drudis.2025.104474","DOIUrl":"10.1016/j.drudis.2025.104474","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 10","pages":"Article 104474"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102475","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
Carbon dots in oncology: multifunctional nanoplatforms for diagnosis, targeted therapy, and drug discovery 肿瘤中的碳点：用于诊断、靶向治疗和药物发现的多功能纳米平台。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104470
Sandra Rodríguez-Varillas , Jorge Espina-Casado , Rosana Badía Laíño , Alfonso Fernández-González , Tania Fontanil López
{"title":"Carbon dots in oncology: multifunctional nanoplatforms for diagnosis, targeted therapy, and drug discovery","authors":"Sandra Rodríguez-Varillas ,&nbsp;Jorge Espina-Casado ,&nbsp;Rosana Badía Laíño ,&nbsp;Alfonso Fernández-González ,&nbsp;Tania Fontanil López","doi":"10.1016/j.drudis.2025.104470","DOIUrl":"10.1016/j.drudis.2025.104470","url":null,"abstract":"<div><div>Carbon dots (CDs) are emerging nanomaterials with unique optical and biological properties that position them as highly promising candidates in precision oncology. Their small size, biocompatibility, fluorescence, and capacity for surface functionalization enable diverse applications, including tumor imaging, targeted drug delivery, gene therapy, and photothermal or photodynamic therapy (PTT/PDT). CDs have demonstrated efficacy in fluorescence and magnetic resonance imaging (MRI), facilitating early tumor detection. As drug carriers and gene delivery systems, they offer controlled and targeted release with reduced toxicity. In addition, CDs support early-phase drug discovery by improving solubility and bioavailability, and enabling real-time tracking. Despite these promising results, their clinical translation remains limited by variability in synthesis methods and an incomplete understanding of their structure–function relationships.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 10","pages":"Article 104470"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051600","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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