Nature Reviews Drug Discovery最新文献_第8页

Insights into new approach methodology innovation: an EMA perspective 对新方法方法创新的见解：EMA视角

Nature Reviews Drug Discovery Pub Date : 2025-03-24 DOI: 10.1038/d41573-025-00052-8

引用次数: 0

Life science ecosystems in Asia: biomedical innovation trends over the past decade 亚洲的生命科学生态系统：过去十年生物医学创新趋势

Nature Reviews Drug Discovery Pub Date : 2025-03-21 DOI: 10.1038/d41573-025-00041-x

引用次数: 0

A new target for cancer cachexia 癌症恶病质的新靶点

Nature Reviews Drug Discovery Pub Date : 2025-03-20 DOI: 10.1038/d41573-025-00054-6

引用次数: 0

Computational drug repurposing: approaches, evaluation of in silico resources and case studies 计算机药物再利用：方法，计算机资源评估和案例研究

Nature Reviews Drug Discovery Pub Date : 2025-03-18 DOI: 10.1038/s41573-025-01164-x

Ziaurrehman Tanoli, Adrià Fernández-Torras, Umut Onur Özcan, Aleksandr Kushnir, Kristen Michelle Nader, Yojana Gadiya, Laura Fiorenza, Aleksandr Ianevski, Markus Vähä-Koskela, Mitro Miihkinen, Umair Seemab, Henri Leinonen, Brinton Seashore-Ludlow, Marianna Tampere, Adelinn Kalman, Flavio Ballante, Emilio Benfenati, Gary Saunders, Swapnil Potdar, Ismael Gómez García, Ricard García-Serna, Carmine Talarico, Andrea Rosario Beccari, Wesley Schaal, Andrea Polo, Susan Costantini, Enrico Cabri, Marc Jacobs, Jani Saarela, Alfredo Budillon, Ola Spjuth, Päivi Östling, Henri Xhaard, Jordi Quintana, Jordi Mestres, Philip Gribbon, Anton E. Ussi, Donald C. Lo, Martin de Kort, Krister Wennerberg, Maddalena Fratelli, Jordi Carreras-Puigvert, Tero Aittokallio

{"title":"Computational drug repurposing: approaches, evaluation of in silico resources and case studies","authors":"Ziaurrehman Tanoli, Adrià Fernández-Torras, Umut Onur Özcan, Aleksandr Kushnir, Kristen Michelle Nader, Yojana Gadiya, Laura Fiorenza, Aleksandr Ianevski, Markus Vähä-Koskela, Mitro Miihkinen, Umair Seemab, Henri Leinonen, Brinton Seashore-Ludlow, Marianna Tampere, Adelinn Kalman, Flavio Ballante, Emilio Benfenati, Gary Saunders, Swapnil Potdar, Ismael Gómez García, Ricard García-Serna, Carmine Talarico, Andrea Rosario Beccari, Wesley Schaal, Andrea Polo, Susan Costantini, Enrico Cabri, Marc Jacobs, Jani Saarela, Alfredo Budillon, Ola Spjuth, Päivi Östling, Henri Xhaard, Jordi Quintana, Jordi Mestres, Philip Gribbon, Anton E. Ussi, Donald C. Lo, Martin de Kort, Krister Wennerberg, Maddalena Fratelli, Jordi Carreras-Puigvert, Tero Aittokallio","doi":"10.1038/s41573-025-01164-x","DOIUrl":"https://doi.org/10.1038/s41573-025-01164-x","url":null,"abstract":"Repurposing of existing drugs for new indications has attracted substantial attention owing to its potential to accelerate drug development and reduce costs. Hundreds of computational resources such as databases and predictive platforms have been developed that can be applied for drug repurposing, making it challenging to select the right resource for a specific drug repurposing project. With the aim of helping to address this challenge, here we overview computational approaches to drug repurposing based on a comprehensive survey of available in silico resources using a purpose-built drug repurposing ontology that classifies the resources into hierarchical categories and provides application-specific information. We also present an expert evaluation of selected resources and three drug repurposing case studies implemented within the Horizon Europe REMEDi4ALL project to demonstrate the practical use of the resources. This comprehensive Review with expert evaluations and case studies provides guidelines and recommendations on the best use of various in silico resources for drug repurposing and establishes a basis for a sustainable and extendable drug repurposing web catalogue.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibrosis: cross-organ biology and pathways to development of innovative drugs 纤维化：跨器官生物学和创新药物开发途径

Nature Reviews Drug Discovery Pub Date : 2025-03-18 DOI: 10.1038/s41573-025-01158-9

Florian Rieder, Laura E. Nagy, Toby M. Maher, Jörg H. W. Distler, Rafael Kramann, Boris Hinz, Marco Prunotto

{"title":"Fibrosis: cross-organ biology and pathways to development of innovative drugs","authors":"Florian Rieder, Laura E. Nagy, Toby M. Maher, Jörg H. W. Distler, Rafael Kramann, Boris Hinz, Marco Prunotto","doi":"10.1038/s41573-025-01158-9","DOIUrl":"https://doi.org/10.1038/s41573-025-01158-9","url":null,"abstract":"Fibrosis is a pathophysiological mechanism involved in chronic and progressive diseases that results in excessive tissue scarring. Diseases associated with fibrosis include metabolic dysfunction-associated steatohepatitis (MASH), inflammatory bowel diseases (IBDs), chronic kidney disease (CKD), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), which are collectively responsible for substantial morbidity and mortality. Although a few drugs with direct antifibrotic activity are approved for pulmonary fibrosis and considerable progress has been made in the understanding of mechanisms of fibrosis, translation of this knowledge into effective therapies continues to be limited and challenging. With the aim of assisting developers of novel antifibrotic drugs, this Review integrates viewpoints of biologists and physician-scientists on core pathways involved in fibrosis across organs, as well as on specific characteristics and approaches to assess therapeutic interventions for fibrotic diseases of the lung, gut, kidney, skin and liver. This discussion is used as a basis to propose strategies to improve the translation of potential antifibrotic therapies.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerating precision oncology by converging pragmatic trials and real-world evidence 通过融合实用试验和现实世界证据，加速精准肿瘤学

Nature Reviews Drug Discovery Pub Date : 2025-03-13 DOI: 10.1038/d41573-025-00047-5

Kjetil Taskén, Piers Mahon

引用次数: 0

Tumour-agnostic kinase inhibitors 与肿瘤无关的激酶抑制剂

Nature Reviews Drug Discovery Pub Date : 2025-03-06 DOI: 10.1038/s41573-025-01147-y

Jacob J. Adashek, Mina Nikanjam, Razelle Kurzrock

{"title":"Tumour-agnostic kinase inhibitors","authors":"Jacob J. Adashek, Mina Nikanjam, Razelle Kurzrock","doi":"10.1038/s41573-025-01147-y","DOIUrl":"https://doi.org/10.1038/s41573-025-01147-y","url":null,"abstract":"Protein kinases are crucial targets for cancer treatment as they orchestrate important signals for oncogenesis and are often aberrantly activated owing to genomic alterations. In the past two decades, multiple kinase inhibitors have been developed, including those that are clinically effective regardless of tumour location, provided that the tumour harbours the aberrantly activated kinase. Consequently, a biomarker-based therapy model, untethered from tumour histology and organ of origin, has been established, which has led to transformative regulatory approvals of tumour-agnostic kinase inhibitors such as larotrectinib, selpercatinib, dabrafenib–trametinib and pemigatinib. However, almost all such approvals are partial in nature, as they do not include both solid and haematological cancers, even if the kinase inhibitor has shown activity in both. Moreover, clinical trials to assess these compounds are challenging because genomic sequencing of hundreds or thousands of tumours may be required to find eligible patients whose malignancy bears the targeted genetic alterations. In this Review, we describe the precision medicine paradigm that has successfully launched tumour-agnostic drug development, concentrating on small-molecule inhibitors that target kinase pathway aberrations, and we discuss the challenges in developing tumour‐agnostic agents.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerating adoption of new approach methodologies in regulatory decision making: an industry perspective 在监管决策中加速采用新方法：一个行业观点

Nature Reviews Drug Discovery Pub Date : 2025-03-06 DOI: 10.1038/d41573-025-00038-6

Andrew S. Robertson, Nahid Latif, Imein Bousnina, Donna Boyce, Kevin Carl, Sean P. Curtis, Jennifer Dudinak, Carlos O. Garner, Michael Garvin, Sabine Luik, Eddie Reilly, Michelle Rohrer, Katrin Rupalla, Jacintha Shenton, Jerry Stewart, Mark Taisey, Raymond C. Votzmeyer, Matthew P. Wagoner, Max Wegner, Kathy Williams

引用次数: 0

Thirty years of NRF2: advances and therapeutic challenges NRF2三十年：进展与治疗挑战

Nature Reviews Drug Discovery Pub Date : 2025-03-04 DOI: 10.1038/s41573-025-01145-0

Donna D. Zhang

引用次数: 0

GPCR drug discovery: new agents, targets and indications GPCR药物发现：新的药物、靶点和适应症

Nature Reviews Drug Discovery Pub Date : 2025-03-03 DOI: 10.1038/s41573-025-01139-y

Javier Sánchez Lorente, Aleksandr V. Sokolov, Gavin Ferguson, Helgi B. Schiöth, Alexander S. Hauser, David E. Gloriam

{"title":"GPCR drug discovery: new agents, targets and indications","authors":"Javier Sánchez Lorente, Aleksandr V. Sokolov, Gavin Ferguson, Helgi B. Schiöth, Alexander S. Hauser, David E. Gloriam","doi":"10.1038/s41573-025-01139-y","DOIUrl":"https://doi.org/10.1038/s41573-025-01139-y","url":null,"abstract":"G protein-coupled receptors (GPCRs) form one of the largest drug target families, reflecting their involvement in numerous pathophysiological processes. In this Review, we analyse drug discovery trends for the GPCR superfamily, covering compounds, targets and indications that have reached regulatory approval or that are being investigated in clinical trials. We find that there are 516 approved drugs targeting GPCRs, making up 36% of all approved drugs. These drugs act on 121 GPCR targets, one-third of all non-sensory GPCRs. Furthermore, 337 agents targeting 133 GPCRs, including 30 novel targets, are being investigated in clinical trials. Notably, 165 of these agents are approved drugs being tested for additional indications and novel agents are increasingly allosteric modulators and biologics. Remarkably, diabetes and obesity drugs targeting GPCRs had sales of nearly US $30 billion in 2023 and the numbers of clinical trials for GPCR modulators in the metabolic diseases, oncology and immunology areas are increasing strongly. Finally, we highlight the potential of untapped target–disease associations and pathway-biased signalling. Overall, this Review provides an up-to-date reference for the drugged and potentially druggable GPCRome to inform future GPCR drug discovery and development.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0