Pub Date : 2024-06-21DOI: 10.1038/d41573-024-00106-3
Ken Garber
Small molecules that block a key protein–protein interaction could change the treatment landscape for many patients with acute leukaemias. Small molecules that block a key protein–protein interaction could change the treatment landscape for many patients with acute leukaemias.
阻断关键蛋白-蛋白相互作用的小分子药物可能会改变许多急性白血病患者的治疗前景。
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Pub Date : 2024-06-19DOI: 10.1038/d41573-024-00105-4
Yvonne Bordon
{"title":"CAR T cells take to the airways","authors":"Yvonne Bordon","doi":"10.1038/d41573-024-00105-4","DOIUrl":"10.1038/d41573-024-00105-4","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 8","pages":"579-579"},"PeriodicalIF":122.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-18DOI: 10.1038/d41573-024-00103-6
Asher Mullard
Biohaven’s BHV-1300 lowered levels of immunoglobulin G in the blood of healthy volunteers — a first clinical demonstration of the potential of a small-molecule extracellular protein degrader. Biohaven’s BHV-1300 lowered levels of immunoglobulin G in the blood of healthy volunteers — a first clinical demonstration of the potential of a small-molecule extracellular protein degrader.
Biohaven 的 BHV-1300 降低了健康志愿者血液中免疫球蛋白 G 的水平--首次临床验证了小分子细胞外蛋白降解剂的潜力。Biohaven 的 BHV-1300 降低了健康志愿者血液中免疫球蛋白 G 的水平，首次在临床上展示了小分子细胞外蛋白降解剂的潜力。
{"title":"Extracellular targeted protein degrader removes antibodies in first test in humans","authors":"Asher Mullard","doi":"10.1038/d41573-024-00103-6","DOIUrl":"10.1038/d41573-024-00103-6","url":null,"abstract":"Biohaven’s BHV-1300 lowered levels of immunoglobulin G in the blood of healthy volunteers — a first clinical demonstration of the potential of a small-molecule extracellular protein degrader. Biohaven’s BHV-1300 lowered levels of immunoglobulin G in the blood of healthy volunteers — a first clinical demonstration of the potential of a small-molecule extracellular protein degrader.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 7","pages":"483-486"},"PeriodicalIF":122.7,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-18DOI: 10.1038/s41573-024-00958-9
Terry Kenakin
Despite advances in chemical, computational and biological sciences, the rate of attrition of drug candidates in clinical development is still high. A key point in the small-molecule discovery process that could provide opportunities to help address this challenge is the pharmacological characterization of hit and lead compounds, culminating in the selection of a drug candidate. Deeper characterization is increasingly important, because the ‘quality’ of drug efficacy, at least for G protein-coupled receptors (GPCRs), is now understood to be much more than activation of commonly evaluated pathways such as cAMP signalling, with many more ‘efficacies’ of ligands that could be harnessed therapeutically. Such characterization is being enabled by novel assays to characterize the complex behaviour of GPCRs, such as biased signalling and allosteric modulation, as well as advances in structural biology, such as cryo-electron microscopy. This article discusses key factors in the assessments of the pharmacology of hit and lead compounds in the context of GPCRs as a target class, highlighting opportunities to identify drug candidates with the potential to address limitations of current therapies and to improve the probability of them succeeding in clinical development. Deeper pharmacological characterization of hit and lead compounds is being enabled by novel assays to characterize target behaviour as well as by advances in structural biology. This article discusses key factors in pharmacological characterization in the context of G protein-coupled receptors as a target class, highlighting opportunities to identify drug candidates with the potential to address limitations of current therapies and to increase the probability of them succeeding in clinical trials.
{"title":"Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition","authors":"Terry Kenakin","doi":"10.1038/s41573-024-00958-9","DOIUrl":"10.1038/s41573-024-00958-9","url":null,"abstract":"Despite advances in chemical, computational and biological sciences, the rate of attrition of drug candidates in clinical development is still high. A key point in the small-molecule discovery process that could provide opportunities to help address this challenge is the pharmacological characterization of hit and lead compounds, culminating in the selection of a drug candidate. Deeper characterization is increasingly important, because the ‘quality’ of drug efficacy, at least for G protein-coupled receptors (GPCRs), is now understood to be much more than activation of commonly evaluated pathways such as cAMP signalling, with many more ‘efficacies’ of ligands that could be harnessed therapeutically. Such characterization is being enabled by novel assays to characterize the complex behaviour of GPCRs, such as biased signalling and allosteric modulation, as well as advances in structural biology, such as cryo-electron microscopy. This article discusses key factors in the assessments of the pharmacology of hit and lead compounds in the context of GPCRs as a target class, highlighting opportunities to identify drug candidates with the potential to address limitations of current therapies and to improve the probability of them succeeding in clinical development. Deeper pharmacological characterization of hit and lead compounds is being enabled by novel assays to characterize target behaviour as well as by advances in structural biology. This article discusses key factors in pharmacological characterization in the context of G protein-coupled receptors as a target class, highlighting opportunities to identify drug candidates with the potential to address limitations of current therapies and to increase the probability of them succeeding in clinical trials.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 8","pages":"626-644"},"PeriodicalIF":122.7,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1038/s41573-024-00993-6
Richard J. Brennan, Stephen Jenkinson, Andrew Brown, Annie Delaunois, Bérengère Dumotier, Malar Pannirselvam, Mohan Rao, Lyn Rosenbrier Ribeiro, Friedemann Schmidt, Alicia Sibony, Yoav Timsit, Vicencia Toledo Sales, Duncan Armstrong, Armando Lagrutta, Scott W. Mittlestadt, Russell Naven, Ravikumar Peri, Sonia Roberts, James M. Vergis, Jean-Pierre Valentin
{"title":"Author Correction: The state of the art in secondary pharmacology and its impact on the safety of new medicines","authors":"Richard J. Brennan, Stephen Jenkinson, Andrew Brown, Annie Delaunois, Bérengère Dumotier, Malar Pannirselvam, Mohan Rao, Lyn Rosenbrier Ribeiro, Friedemann Schmidt, Alicia Sibony, Yoav Timsit, Vicencia Toledo Sales, Duncan Armstrong, Armando Lagrutta, Scott W. Mittlestadt, Russell Naven, Ravikumar Peri, Sonia Roberts, James M. Vergis, Jean-Pierre Valentin","doi":"10.1038/s41573-024-00993-6","DOIUrl":"10.1038/s41573-024-00993-6","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 7","pages":"563-563"},"PeriodicalIF":122.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41573-024-00993-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-11DOI: 10.1038/d41573-024-00096-2
Asher Mullard
Cigall Kadoch, a cancer researcher at Dana-Farber Cancer Institute and co-founder of Foghorn Therapeutics, discusses the case for a new wave of epigenetic drugs, targeting chromatin remodelling complexes. Cigall Kadoch, a cancer researcher at Dana-Farber Cancer Institute and co-founder of Foghorn Therapeutics, discusses the case for a new wave of epigenetic drugs, targeting chromatin remodelling complexes.
{"title":"Chromatin-targeted drug discovery at “a very special moment”","authors":"Asher Mullard","doi":"10.1038/d41573-024-00096-2","DOIUrl":"10.1038/d41573-024-00096-2","url":null,"abstract":"Cigall Kadoch, a cancer researcher at Dana-Farber Cancer Institute and co-founder of Foghorn Therapeutics, discusses the case for a new wave of epigenetic drugs, targeting chromatin remodelling complexes. Cigall Kadoch, a cancer researcher at Dana-Farber Cancer Institute and co-founder of Foghorn Therapeutics, discusses the case for a new wave of epigenetic drugs, targeting chromatin remodelling complexes.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 7","pages":"490-491"},"PeriodicalIF":122.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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