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Philanthropic drug development: understanding its importance, mechanisms, and future prospects.
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-21 DOI: 10.1016/j.drudis.2025.104298
Marc Reichel, Eva M Murauer, Martin Steiner, Christoph Coch, Hubert Trübel
{"title":"Philanthropic drug development: understanding its importance, mechanisms, and future prospects.","authors":"Marc Reichel, Eva M Murauer, Martin Steiner, Christoph Coch, Hubert Trübel","doi":"10.1016/j.drudis.2025.104298","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104298","url":null,"abstract":"<p><p>Philanthropic drug development (PDD) addresses gaps in traditional pharmaceutical innovation, particularly for rare and underserved diseases. Cost and timeline challenges discourage new investments, especially in niche therapeutic areas. Patient organizations (POs) are uniquely positioned to help to reduce development challenges by providing expertise, supporting early research, fostering collaborations, and driving patient-centered clinical trials. PDD relies on effective partnerships between POs, pharmaceutical companies, and other stakeholders, ensuring that patient perspectives inform the drug development process. PDD is poised to relieve the pressure on the traditional drug development process and thereby foster beneficial patient-focused innovations. In doing so, PDD allows pharmaceutical companies to expand their drug development activities into commercially unrewarding {AuQ: Edit OK?} areas, diversifying their portfolios beyond competitive fields.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104298"},"PeriodicalIF":6.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027497","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
Death ligand receptor (DLR) signaling: Its non-apoptotic functions in cancer and the consequences of DLR-directed therapies.
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-20 DOI: 10.1016/j.drudis.2025.104299
Khalid Rashid, Holger Kalthoff, Sarki A Abdulkadir, Dieter Adam
{"title":"Death ligand receptor (DLR) signaling: Its non-apoptotic functions in cancer and the consequences of DLR-directed therapies.","authors":"Khalid Rashid, Holger Kalthoff, Sarki A Abdulkadir, Dieter Adam","doi":"10.1016/j.drudis.2025.104299","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104299","url":null,"abstract":"<p><p>Death ligands (DLs), particularly tumor necrosis factor alpha (TNF-α), FAS ligand (FASL), and TNF-related apoptosis-inducing ligand (TRAIL), collectively termed TFT, are pivotal members of the TNF superfamily. While traditionally linked to apoptosis, TFT proteins have emerged as key regulators of various non-apoptotic processes. This review summarizes the non-apoptotic functions of TFT in cancer and explores the intricate crosstalk signaling pathways and their impact on nuclear factor kappa B (NF-κB) signaling, inflammation, and pro-tumorigenic function. It also highlights the potential connections and hurdles that exist in translating synthetic lethality strategies involving DLs into clinical applications. Lastly, it discusses the challenges and opportunities associated with TFT-targeted therapeutic strategies for both malignant and non-malignant diseases.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104299"},"PeriodicalIF":6.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021440","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
Artificial intelligence in peptide-based drug design.
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-20 DOI: 10.1016/j.drudis.2025.104300
Silong Zhai, Tiantao Liu, Shaolong Lin, Dan Li, Huanxiang Liu, Xiaojun Yao, Tingjun Hou
{"title":"Artificial intelligence in peptide-based drug design.","authors":"Silong Zhai, Tiantao Liu, Shaolong Lin, Dan Li, Huanxiang Liu, Xiaojun Yao, Tingjun Hou","doi":"10.1016/j.drudis.2025.104300","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104300","url":null,"abstract":"<p><p>Protein-protein interactions (PPIs) are fundamental to a variety of biological processes, but targeting them with small molecules is challenging because of their large and complex interaction interfaces. However, peptides have emerged as highly promising modulators of PPIs, because they can bind to protein surfaces with high affinity and specificity. Nonetheless, computational peptide design remains difficult, hindered by the intrinsic flexibility of peptides and the substantial computational resources required. Recent advances in artificial intelligence (AI) are paving new paths for peptide-based drug design. In this review, we explore the advanced deep generative models for designing target-specific peptide binders, highlight key challenges, and offer insights into the future direction of this rapidly evolving field.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104300"},"PeriodicalIF":6.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021436","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
Is ChatGPT ready for public use in organ-specific drug toxicity research?
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-20 DOI: 10.1016/j.drudis.2025.104297
Skylar Connor, Leihong Wu, Ruth A Roberts, Weida Tong
{"title":"Is ChatGPT ready for public use in organ-specific drug toxicity research?","authors":"Skylar Connor, Leihong Wu, Ruth A Roberts, Weida Tong","doi":"10.1016/j.drudis.2025.104297","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104297","url":null,"abstract":"<p><p>The growing impact of large language models (LLMs), such as ChatGPT, prompts questions about the reliability of their application in public health. We compared drug toxicity assessments by GPT-4 for liver, heart, and kidney against expert assessments using US Food and Drug Administration (FDA) drug-labeling documents. Two approaches were assessed: a 'General prompt', mimicking the conversational style used by the general public, and an 'Expert prompt' engineered to represent an approach of an expert. The Expert prompt achieved higher accuracy (64-75%) compared with the General prompt (48-72%), but the overall performance was moderate, indicating that caution is needed when using GPT-4 for public health. To improve reliability, an advanced framework ,such as Retrieval Augmented Generation (RAG), might be required to leverage knowledge embedded in GPT-4.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104297"},"PeriodicalIF":6.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021448","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
Albendazole-induced liver injury in children: a cause for concern? 阿苯达唑致儿童肝损伤：值得关注的原因？
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-18 DOI: 10.1016/j.drudis.2025.104296
Devaraj Ezhilarasan, Mustapha Najimi
{"title":"Albendazole-induced liver injury in children: a cause for concern?","authors":"Devaraj Ezhilarasan, Mustapha Najimi","doi":"10.1016/j.drudis.2025.104296","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104296","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104296"},"PeriodicalIF":6.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997027","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 Value in Failure. 失败中的值。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-18 DOI: 10.1016/j.drudis.2025.104294
Alastair D G Lawson
{"title":"The Value in Failure.","authors":"Alastair D G Lawson","doi":"10.1016/j.drudis.2025.104294","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104294","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104294"},"PeriodicalIF":6.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997222","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
Applications and emerging challenges of single-cell RNA sequencing technology in tumor drug discovery. 单细胞RNA测序技术在肿瘤药物发现中的应用和新挑战。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-17 DOI: 10.1016/j.drudis.2025.104290
Lu Zhang, Yueying Yang, Jianjun Tan
{"title":"Applications and emerging challenges of single-cell RNA sequencing technology in tumor drug discovery.","authors":"Lu Zhang, Yueying Yang, Jianjun Tan","doi":"10.1016/j.drudis.2025.104290","DOIUrl":"10.1016/j.drudis.2025.104290","url":null,"abstract":"<p><p>Current therapeutic drugs are inadequate for curing tumors, highlighting the need for novel tumor drugs. The advancement of single-cell RNA sequencing (scRNA-seq) technology offers new opportunities for tumor drug discovery. This technology allows us to explore tumor heterogeneity and developmental mechanisms at the single-cell level. In this review, we outline the application of scRNA-seq in tumor drug discovery stages, including elucidating tumor mechanisms, identifying targets, screening drugs, and understanding drug action and resistance. We also discuss the challenges and future prospects of using scRNA-seq in drug development, providing a scientific foundation for advancing tumor therapies.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104290"},"PeriodicalIF":6.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997219","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
Competition of regulatory ecosystems in approving medicines: policy implications in the case of Europe. 审批药品时监管生态系统的竞争：对欧洲的政策影响。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-17 DOI: 10.1016/j.drudis.2025.104295
Pedro Franco, Stefan Haefliger
{"title":"Competition of regulatory ecosystems in approving medicines: policy implications in the case of Europe.","authors":"Pedro Franco, Stefan Haefliger","doi":"10.1016/j.drudis.2025.104295","DOIUrl":"https://doi.org/10.1016/j.drudis.2025.104295","url":null,"abstract":"<p><p>The competition between business ecosystems is relevant not only for strategic management, but also for health policy and regulators. Regulation is one key factor in ecosystem competition, and government and regulatory bodies implement new pharmaceutical legislations, policies, and guidelines contributing to business environments capable of attracting startups, biotech firms, and pharmaceutical industry investments in innovative medicines and technologies. Implications for patients and societal welfare require a thorough analysis of strategies aimed at enhancing the competitive advantage of the European Union (EU) in attracting pharmaceutical companies to prioritize the submission of their innovative medicines. This analysis is essential for ensuring that patients have timely access to new treatments, that society benefits from advances in healthcare, and could foster the competitive advantage of the European regulatory ecosystem. Here, we present data from 65 interviews with pharmaceutical industry professionals, offering direct insights into regulatory ecosystem competition and global health policy. Our report underscores the necessity for effective strategies that enhance the competitive advantage of the European regulatory system.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104295"},"PeriodicalIF":6.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997220","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 for the identification of novel metal-binding pharmacophores: advances and challenges. 识别新型金属结合药物载体的计算方法：进展与挑战。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-11 DOI: 10.1016/j.drudis.2025.104293
Guoli Xiong, Zhiyan Xiao
{"title":"Computational approaches for the identification of novel metal-binding pharmacophores: advances and challenges.","authors":"Guoli Xiong, Zhiyan Xiao","doi":"10.1016/j.drudis.2025.104293","DOIUrl":"10.1016/j.drudis.2025.104293","url":null,"abstract":"<p><p>Metalloenzymes are important therapeutic targets for a variety of human diseases. Computational approaches have recently emerged as effective tools to understand metal-ligand interactions and expand the structural diversity of both metalloenzyme inhibitors (MIs) and metal-binding pharmacophores (MBPs). In this review, we highlight key advances in currently available fine-tuning modeling methods and data-driven cheminformatic approaches. We also discuss major challenges to the recognition of novel MBPs and MIs. The evidence provided herein could expedite future computational efforts to guide metalloenzyme-based drug discovery.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104293"},"PeriodicalIF":6.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976922","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
Benchmarking R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006-2022). 领先制药公司研发成功率标杆化：2006-2022年FDA批准的实证分析。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-01-11 DOI: 10.1016/j.drudis.2025.104291
Alexander Schuhmacher, Markus Hinder, Elazar Brief, Oliver Gassmann, Dominik Hartl
{"title":"Benchmarking R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006-2022).","authors":"Alexander Schuhmacher, Markus Hinder, Elazar Brief, Oliver Gassmann, Dominik Hartl","doi":"10.1016/j.drudis.2025.104291","DOIUrl":"10.1016/j.drudis.2025.104291","url":null,"abstract":"<p><p>Previous analyses provide an industry benchmark of ∼10% for the success rate in clinical development. However, prior analyses were limited by a narrow timeframe, a diverse research focus, biases in phase-to-phase transition methodology or a focus on specific use cases. We calculated unbiased input:output ratios (Phase I to FDA new drug approval) to analyze the likelihood of first approval using data from clinicaltrials.gov, encompassing a total of 2092 active ingredients, 19 927 clinical trials conducted by 18 leading pharmaceutical companies (2006-2022) and 274 new drug approvals. Our study reveals an average likelihood of first approval rate of 14.3% across leading research-based pharmaceutical companies, broadly ranging from 8% to 23%.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104291"},"PeriodicalIF":6.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976919","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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