Nature Reviews Drug Discovery最新文献

Lasso peptide targets drug-resistant bacteria Lasso肽靶向耐药细菌

Nature Reviews Drug Discovery Pub Date : 2025-05-02 DOI: 10.1038/d41573-025-00075-1

引用次数: 0

Targeting RNA structure to treat prostate cancer 靶向RNA结构治疗前列腺癌

Nature Reviews Drug Discovery Pub Date : 2025-05-02 DOI: 10.1038/d41573-025-00077-z

引用次数: 0

Application of new approach methodologies for nonclinical safety assessment of drug candidates 新方法方法在候选药物非临床安全性评估中的应用

Nature Reviews Drug Discovery Pub Date : 2025-05-02 DOI: 10.1038/s41573-025-01182-9

Mario Beilmann, Karissa Adkins, Harrie C. M. Boonen, Philip Hewitt, Wenyue Hu, Robert Mader, Susanne Moore, Payal Rana, Thomas Steger-Hartmann, Remi Villenave, Terry van Vleet

{"title":"Application of new approach methodologies for nonclinical safety assessment of drug candidates","authors":"Mario Beilmann, Karissa Adkins, Harrie C. M. Boonen, Philip Hewitt, Wenyue Hu, Robert Mader, Susanne Moore, Payal Rana, Thomas Steger-Hartmann, Remi Villenave, Terry van Vleet","doi":"10.1038/s41573-025-01182-9","DOIUrl":"https://doi.org/10.1038/s41573-025-01182-9","url":null,"abstract":"The development of new approach methodologies (NAMs) and advances with in vitro testing systems have prompted revisions in regulatory guidelines and inspired dedicated in vitro/ex vivo studies for nonclinical safety assessment. This Review by a safety reflection initiative subgroup of the European Federation of Pharmaceutical Industries and Associations (EFPIA)/Preclinical Development Expert Group (PDEG) summarizes the current state and potential application of in vitro studies using human-derived material for safety assessment in drug development. It focuses on case studies from recent projects in which animal models alone proved to be limited or inadequate for safety testing. It further highlights four categories of drug candidates for which alternative in vitro approaches are applicable and discusses progress in using in vitro testing solutions for safety assessment in these categories. Finally, the article highlights new risk assessment strategies, initiatives and consortia promoting the advancement of NAMs. This collective work is meant to encourage the use of NAMs for more human-relevant safety assessment, which should ultimately result in reduced animal testing for drug development.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901259","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

TIM-3 regulates microglial function TIM-3调节小胶质细胞功能

Nature Reviews Drug Discovery Pub Date : 2025-05-02 DOI: 10.1038/d41573-025-00078-y

引用次数: 0

Understanding LAG3 immune checkpoint function 了解LAG3免疫检查点功能

Nature Reviews Drug Discovery Pub Date : 2025-05-02 DOI: 10.1038/d41573-025-00076-0

引用次数: 0

Ramping up mitochondrial DNA replication 加快线粒体DNA的复制

Nature Reviews Drug Discovery Pub Date : 2025-05-02 DOI: 10.1038/d41573-025-00079-x

引用次数: 0

GLP-1-based therapies for diabetes, obesity and beyond 以glp -1为基础的糖尿病、肥胖症及其他疾病的治疗

Nature Reviews Drug Discovery Pub Date : 2025-04-25 DOI: 10.1038/s41573-025-01183-8

Daniel J. Drucker

{"title":"GLP-1-based therapies for diabetes, obesity and beyond","authors":"Daniel J. Drucker","doi":"10.1038/s41573-025-01183-8","DOIUrl":"https://doi.org/10.1038/s41573-025-01183-8","url":null,"abstract":"Glucagon-like peptide 1 (GLP-1)-based therapies, such as semaglutide and tirzepatide, represent highly effective treatment options for people with type 2 diabetes and obesity, enabling effective control of glucose and weight loss, while reducing cardiovascular and renal morbidity and mortality. The success of these medicines has spurred development of next-generation GLP-1-based drugs, promising greater weight loss, improved tolerability and additional options for the route and frequency of dosing. This Review profiles established and emerging GLP-1-based medicines, discussing optimization of pharmacokinetics and tolerability, engagement of new therapeutically useful pathways and safety aspects. Structurally unique GLP-1-based medicines that achieve substantially greater and rapid weight loss may impact musculoskeletal health, providing a rationale for therapeutics that more selectively target adipose tissue loss while preserving muscle mass and strength. Ongoing clinical trials in peripheral vascular disease, neuropsychiatric and substance use disorders, metabolic liver disease, arthritis, hypertension and neurodegenerative disorders may broaden indications for GLP-1-based therapeutics. ","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872211","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

New antifungal tackles drug-resistant infections 新的抗真菌药物治疗耐药感染

Nature Reviews Drug Discovery Pub Date : 2025-04-24 DOI: 10.1038/d41573-025-00074-2

引用次数: 0

The impact of accelerated drug marketing registration procedures on the review and approval of new drugs in China 加快药品上市注册程序对中国新药审批的影响

Nature Reviews Drug Discovery Pub Date : 2025-04-23 DOI: 10.1038/d41573-025-00070-6

引用次数: 0

Shaping secondary pharmacology panels of the future: evolving target selection criteria for safety panels 塑造未来的二级药理学小组：发展安全小组的目标选择标准

Nature Reviews Drug Discovery Pub Date : 2025-04-22 DOI: 10.1038/s41573-025-01184-7

Friedemann Schmidt, Richard J. Brennan, Steve Jenkinson, Jean-Pierre Valentin

{"title":"Shaping secondary pharmacology panels of the future: evolving target selection criteria for safety panels","authors":"Friedemann Schmidt, Richard J. Brennan, Steve Jenkinson, Jean-Pierre Valentin","doi":"10.1038/s41573-025-01184-7","DOIUrl":"https://doi.org/10.1038/s41573-025-01184-7","url":null,"abstract":"We appreciate the thoughtful commentary by Maciag and Karamyan1 on our 2024 publication ‘The state of the art in secondary pharmacology and its impact on the safety of new medicines’2. In this paper, we reviewed secondary pharmacology data and profiling strategies from 18 pharmaceutical companies and recommended the implementation of an expanded core safety panel consisting of 77 diverse targets (Safety-77). The main aim of such screening panels is to identify potential human safety liabilities of novel molecules across all indications and chemotypes. To serve its purpose, the panel was balanced with respect to diversity of target families and mechanisms of toxicities, but it was also kept feasible with respect to its size.Maciag and Karamyan highlight the underrepresentation of non-kinase enzymes in our recommended assay panels and suggest the consideration of non-kinase enzymes such as neprilysin, cathepsins, carbonic anhydrases, thromboxane A synthase and xanthine oxidase due to risks of adverse events associated with activity against these enzymes. Studies by regulatory agencies have shown that inhibition of enzymes could be implicated in adverse events and that enzymes have comparable or higher hit rates than other targets (see Related links).","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858229","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