{"title":"The US biosimilars market after one decade","authors":"","doi":"10.1038/d41573-025-00101-2","DOIUrl":"https://doi.org/10.1038/d41573-025-00101-2","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587019","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}
{"title":"FDA approves twice-yearly capsid inhibitor for HIV prevention","authors":"","doi":"10.1038/d41573-025-00117-8","DOIUrl":"https://doi.org/10.1038/d41573-025-00117-8","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578124","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}
{"title":"Dual-payload ADCs move into first oncology clinical trials","authors":"","doi":"10.1038/d41573-025-00121-y","DOIUrl":"https://doi.org/10.1038/d41573-025-00121-y","url":null,"abstract":"Two dual-payload antibody–drug conjugates are now in the clinic for cancer, with many more on the way.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578126","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}
Anita Rácz, Levente M. Mihalovits, Maximilian Beckers, Nikolas Fechner, Nikolaus Stiefl, Finton Sirockin, William McCoull, Emma Evertsson, Malin Lemurell, Gergely Makara, György M. Keserű
{"title":"The changing landscape of medicinal chemistry optimization","authors":"Anita Rácz, Levente M. Mihalovits, Maximilian Beckers, Nikolas Fechner, Nikolaus Stiefl, Finton Sirockin, William McCoull, Emma Evertsson, Malin Lemurell, Gergely Makara, György M. Keserű","doi":"10.1038/s41573-025-01225-1","DOIUrl":"https://doi.org/10.1038/s41573-025-01225-1","url":null,"abstract":"<p>The goal of a small-molecule drug discovery campaign is the development of chemical entities that fulfil the criteria of the target product profile for progression into clinical trials. This objective is realized through multiparameter medicinal chemistry optimization, typically by identifying the compounds at the hit stage with molecular properties that provide a high chance of subsequent success, and then iteratively optimizing the properties, often in parallel, to identify leads and, ultimately, drug candidates. To assess the impact of medicinal chemistry optimizations on molecular properties, a set of new drug candidates reported in the literature between 2015 and 2022, and their corresponding hit and lead compounds, were analysed, and compared with a set of drug candidates identified between 2000 and 2010, and their corresponding hits and leads. This analysis was complemented by similar analyses of the internal medicinal chemistry programmes pursued at AstraZeneca and Novartis. Here, we highlight and discuss the implications of the observed trends, which include shifts in key physicochemical properties and strategic changes in medicinal chemistry programmes.</p>","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568759","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}
{"title":"Stealthy polymer attacks Gram-negative bacteria","authors":"","doi":"10.1038/d41573-025-00118-7","DOIUrl":"https://doi.org/10.1038/d41573-025-00118-7","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533713","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}
{"title":"Targeting the Hippo pathway in cancer","authors":"Kieran F. Harvey, Tracy T. Tang","doi":"10.1038/s41573-025-01234-0","DOIUrl":"https://doi.org/10.1038/s41573-025-01234-0","url":null,"abstract":"<p>The Hippo pathway is a highly conserved signalling network that controls tissue growth and cell fate, responding to physical properties of the tissue microenvironment and cell biological features such as adhesion and polarity. Hippo signalling perturbation is associated with several human diseases, particularly various solid cancers. Hippo pathway-targeted therapies are beginning to emerge for the treatment of cancer, most of which are focused on disrupting the ability of the YAP and TAZ transcription co-activator proteins to promote transcription of genes with their cognate TEAD1–4 DNA binding proteins. Recently, TEAD inhibitors have shown promise in a phase I clinical trial in cancers that are enriched for Hippo pathway mutations, such as mesothelioma. Moreover, Hippo pathway-targeted therapies have great potential to be combined with RAS–MAPK pathway inhibitors, given the close functional relationship that these signalling pathways share in development and disease.</p>","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515556","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}
{"title":"FDA approves first factor XIIa inhibitor, for hereditary angioedema","authors":"","doi":"10.1038/d41573-025-00114-x","DOIUrl":"https://doi.org/10.1038/d41573-025-00114-x","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500575","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}
{"title":"Enhancing CAR-T cell efficacy through IFN ablation","authors":"","doi":"10.1038/d41573-025-00115-w","DOIUrl":"https://doi.org/10.1038/d41573-025-00115-w","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488528","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}
Marcel P. Trefny, Guido Kroemer, Laurence Zitvogel, Sebastian Kobold
{"title":"Metabolites as agents and targets for cancer immunotherapy","authors":"Marcel P. Trefny, Guido Kroemer, Laurence Zitvogel, Sebastian Kobold","doi":"10.1038/s41573-025-01227-z","DOIUrl":"https://doi.org/10.1038/s41573-025-01227-z","url":null,"abstract":"<p>The depletion or accumulation of metabolites in the tumour microenvironment is one of the hallmarks of cancer, but targeting cancer cell metabolism therapeutically must also take into account the impact on metabolic pathways in immune cells. As we understand more about immunometabolism, opportunities arise for synergies between agents that modulate metabolism and immunotherapy. In this Review, we discuss the pivotal role of metabolic pathways in both cancer and immune cells in shaping the tumour microenvironment. We survey major anabolic and catabolic pathways and discuss how metabolic modulators and dietary nutrients can improve the anticancer immune response and overcome drug resistance mechanisms. Agents in the clinic include inhibitors of the adenosine and tryptophan pathways, and we discuss opportunities and challenges for successful drug development in the context of immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapies.</p>","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"249 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488530","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}
{"title":"A neonatal window for in vivo gene therapy in haematopoietic stem cells","authors":"","doi":"10.1038/d41573-025-00116-9","DOIUrl":"https://doi.org/10.1038/d41573-025-00116-9","url":null,"abstract":"Discover the world’s best science and medicine | Nature.com","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488529","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}
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