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Sotatercept in pulmonary arterial hypertension. 索特塞普治疗肺动脉高压。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-16 DOI: 10.1016/j.tips.2025.04.008
Jean-Luc Cracowski, Charles Khouri
{"title":"Sotatercept in pulmonary arterial hypertension.","authors":"Jean-Luc Cracowski, Charles Khouri","doi":"10.1016/j.tips.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.008","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094870","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}
引用次数: 0
The frameshifting element in coronaviruses: structure, function, and potential as a therapeutic target. 冠状病毒中的移框元件：结构、功能和作为治疗靶点的潜力
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-16 DOI: 10.1016/j.tips.2025.04.003
Qi Li, Qian Wang, Rui Wang, Liangren Zhang, Zhenming Liu
{"title":"The frameshifting element in coronaviruses: structure, function, and potential as a therapeutic target.","authors":"Qi Li, Qian Wang, Rui Wang, Liangren Zhang, Zhenming Liu","doi":"10.1016/j.tips.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.003","url":null,"abstract":"<p><p>The frameshifting element (FSE) comprises a slippery heptanucleotide sequence followed by a downstream RNA structure, such as a pseudoknot or stem-loop. Found in various RNA viruses, FSE regulates viral replication via programmed -1 ribosomal frameshifting (-1 PRF), making it a potential broad-spectrum antiviral target. Advances in RNA structural analysis have elucidated the dynamic conformations and cross-viral diversity of FSE, with the SARS-CoV-2 outbreak further highlighting its role in viral replication. Efforts to develop antiviral drugs targeting FSE have progressed through virtual and phenotypic screening. In this review, we explore the evolution, structure, and function of FSE in coronaviruses, evaluate recent advances in FSE-targeted drug development, and discuss their design advantages, efficacy, and challenges, providing insights for future antiviral strategies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094942","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}
引用次数: 0
Developmental toxicity: artificial intelligence-powered assessments. 发育毒性：人工智能驱动的评估。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-15 DOI: 10.1016/j.tips.2025.04.005
Tong Wang, Xuelian Jia, Lauren M Aleksunes, Hui Shen, Hong-Wen Deng, Hao Zhu
{"title":"Developmental toxicity: artificial intelligence-powered assessments.","authors":"Tong Wang, Xuelian Jia, Lauren M Aleksunes, Hui Shen, Hong-Wen Deng, Hao Zhu","doi":"10.1016/j.tips.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.005","url":null,"abstract":"<p><p>Regulatory agencies require comprehensive toxicity testing for prenatal drug exposure, including new drugs in development, to reduce concerns about developmental toxicity, that is, drug-induced toxicity and adverse effects in pregnant women and fetuses. However, defining developmental toxicity endpoints and optimal analysis of associated public big data remain challenging. Recently, artificial intelligence (AI) approaches have had a critical role in analyzing complex, high-dimensional data, uncovering subtle relationships between chemical exposures and associated developmental risks. Here, we present an overview of major big data resources and data-driven models that focus on predicting various toxicity endpoints. We also highlight emerging, interpretable AI models that integrate multimodal data and domain knowledge to reveal toxic mechanisms underlying complex endpoints, and outline a potential framework that leverages multiple interpretable models to comprehensively evaluate chemical-induced developmental toxicity.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080572","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}
引用次数: 0
Givinostat: a histone deacetylase inhibitor for Duchenne muscular dystrophy. 吉维司他：一种治疗杜氏肌营养不良的组蛋白去乙酰化酶抑制剂。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-15 DOI: 10.1016/j.tips.2025.04.006
Melis Sucuoglu, Serkan Kir
{"title":"Givinostat: a histone deacetylase inhibitor for Duchenne muscular dystrophy.","authors":"Melis Sucuoglu, Serkan Kir","doi":"10.1016/j.tips.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.006","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086112","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}
引用次数: 0
Phylogeny-guided discovery of new antifungals. 系统发育引导下发现新的抗真菌药物。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-14 DOI: 10.1016/j.tips.2025.04.004
Nicolas Papon, Vincent Courdavault, Vishnu Chaturvedi
{"title":"Phylogeny-guided discovery of new antifungals.","authors":"Nicolas Papon, Vincent Courdavault, Vishnu Chaturvedi","doi":"10.1016/j.tips.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.004","url":null,"abstract":"<p><p>Fungal infections are increasing globally, with limited antifungal classes, drug toxicity issues, and the rapid emergence of multidrug resistance (MDR). By using a glycosyltransferase phylogeny-guided strategy, Deng and colleagues recently identified a new broad-spectrum polyene macrolide active against many fungal pathogens, with a novel mechanism of action and excellent safety profile.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080574","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}
引用次数: 0
Targeting the NLRP3 inflammasome for inflammatory disease therapy. 靶向NLRP3炎性小体用于炎性疾病治疗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-14 DOI: 10.1016/j.tips.2025.04.007
Julia Elise Cabral, Anna Wu, Haitian Zhou, Minh Anh Pham, Sophia Lin, Reginald McNulty
{"title":"Targeting the NLRP3 inflammasome for inflammatory disease therapy.","authors":"Julia Elise Cabral, Anna Wu, Haitian Zhou, Minh Anh Pham, Sophia Lin, Reginald McNulty","doi":"10.1016/j.tips.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.007","url":null,"abstract":"<p><p>The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a megadalton complex implicated in numerous inflammation-driven diseases including COVID-19, Alzheimer's disease, and gout. Although past efforts have focused on inhibiting IL-1β downstream of NLRP3 activation using drugs such as canakinumab, no FDA-approved NLRP3-targeted inhibitors are currently available. MCC950, a direct NLRP3 inhibitor, showed promise but exhibited off-target effects. Recent research has focused on optimizing the sulfonylurea-based MCC950 scaffold by leveraging recent structural and medicinal chemistry insights into the NLRP3 nucleotide-binding and oligomerization (NACHT) domain to improve solubility and clinical efficacy. In addition, oxidized DNA (oxDNA) has emerged as a key inflammasome trigger, and molecules targeting the pyrin domain have shown promise in inhibiting NLRP3 activation. This review discusses the role of NLRP3 in inflammation-related diseases, the status of ongoing clinical trials, and emerging small-molecule therapeutics targeting NLRP3.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080576","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}
引用次数: 0
Efferocytosis in inflammatory bone disorders. 炎性骨疾病中的Efferocytosis。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-09 DOI: 10.1016/j.tips.2025.04.001
Linlin Wen, Rongrong Ye, Wenhao Zhai, Daowei Li, Hongchen Sun
{"title":"Efferocytosis in inflammatory bone disorders.","authors":"Linlin Wen, Rongrong Ye, Wenhao Zhai, Daowei Li, Hongchen Sun","doi":"10.1016/j.tips.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.001","url":null,"abstract":"<p><p>Efferocytosis, the clearance of apoptotic cells (ACs) by phagocytes, is crucial for bone homeostasis and immune balance. This tightly regulated process depends on molecular markers such as phosphatidylserine on ACs and MERTK on phagocytes. In the bone microenvironment, multiple cell types participate in efferocytosis, including osteal macrophages, mesenchymal stem cells, osteoblasts, and osteoclasts, directly influencing bone remodeling and immune responses. Impaired efferocytosis disrupts bone turnover, exacerbates inflammation, and contributes to inflammatory bone diseases. Despite its recognized importance, the precise mechanisms regulating efferocytosis in osteoimmunology remain underexplored, including specific signaling pathways, cell-specific interactions, and therapeutic applications. Recent advances highlight the therapeutic potential of targeting efferocytosis using modalities and biomaterial-based strategies. This review systematically examines the role of efferocytosis in osteoimmunology, discusses key challenges in its therapeutic translation, and explores emerging strategies to optimize efferocytosis-based interventions for inflammatory bone disorders.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062160","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}
引用次数: 0
Molecular glue meets antibody: next-generation antibody-drug conjugates. 分子胶与抗体结合：新一代抗体-药物偶联物。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-08 DOI: 10.1016/j.tips.2025.04.002
Yiran Tao, Ying Lu, Bin Yu, Yuxi Wang
{"title":"Molecular glue meets antibody: next-generation antibody-drug conjugates.","authors":"Yiran Tao, Ying Lu, Bin Yu, Yuxi Wang","doi":"10.1016/j.tips.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.002","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have revolutionized oncology by enabling the delivery of cytotoxic agents. However, persistent limitations in payload diversity and emerging drug-resistance mechanisms have spurred investigations into innovative payload modalities. Molecular glue-antibody conjugates (MACs), which utilize molecular glues as payloads, represent a groundbreaking advance in this field. By leveraging the catalytic, event-driven nature of molecular glues, MACs offer enhanced efficacy, reduced off-target effects, and an improved therapeutic index. Two MACs are now in clinical trials. This review explores MAC mechanisms, advances, and potential to surpass traditional ADCs and molecular glues, while addressing development challenges and future directions.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987953","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}
引用次数: 0
Monitoring neurodegeneration through brain-derived extracellular vesicles in biofluids. 通过生物体液中的脑源性细胞外囊泡监测神经变性。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-30 DOI: 10.1016/j.tips.2025.03.006
Francesca Torrini, Marcos Gil-Garcia, Jacopo Cardellini, Roberto Frigerio, Manuela Basso, Alessandro Gori, Paolo Arosio
{"title":"Monitoring neurodegeneration through brain-derived extracellular vesicles in biofluids.","authors":"Francesca Torrini, Marcos Gil-Garcia, Jacopo Cardellini, Roberto Frigerio, Manuela Basso, Alessandro Gori, Paolo Arosio","doi":"10.1016/j.tips.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.006","url":null,"abstract":"<p><p>The identification of neurodegenerative disease (ND) biomarkers in easily accessible body fluids is crucial in the fight against this class of disorders. Brain-derived extracellular vesicles (BDEVs) have gained attention as nanoscale carriers of molecular information and bioactive molecules that reflect the status of their source cells. By crossing the blood-brain barrier (BBB), BDEVs can transfer these biomolecular signatures to peripheral biofluids, setting the scene for their use as ND biomarkers. In this review, we explore the role of BDEVs in liquid biopsy as a promising route for early ND diagnosis, as well as patient stratification and follow-up, with a particular focus on their ability to transport misfolded proteins and protein aggregates, major actors in neurodegeneration development. We also discuss the link between the physicochemical properties of BDEVs and the potential insights gained into NDs, highlighting both challenges and opportunities associated with the use of BDEVs for ND diagnostics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"46 5","pages":"468-479"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033669","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}
引用次数: 0
The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery. BiP和Grp94的结构和功能动力学：治疗发现的机会。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-18 DOI: 10.1016/j.tips.2025.03.004
Ikponwmosa Obaseki, Chioma C Ndolo, Ayodeji A Adedeji, Hannah O Popoola, Andrea N Kravats
{"title":"The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery.","authors":"Ikponwmosa Obaseki, Chioma C Ndolo, Ayodeji A Adedeji, Hannah O Popoola, Andrea N Kravats","doi":"10.1016/j.tips.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.004","url":null,"abstract":"<p><p>Binding immunoglobulin protein (BiP) and glucose-regulated protein 94 (Grp94) are endoplasmic reticulum (ER)-localized molecular chaperones that ensure proper protein folding and maintain protein homeostasis. However, overexpression of these chaperones during ER stress can contribute to disease progression in numerous pathologies. Although these chaperones represent promising therapeutic targets, their inhibition has been challenged by gaps in understanding of targetable chaperone features and their complex biology. To overcome these challenges, a new assay has been developed to selectively target BiP, and compounds that exploit subtle conformational changes of Grp94 have been designed. This review summarizes recent advances in elucidating structural and functional dynamics of BiP and Grp94. We explore leveraging this information to develop novel therapeutic interventions. Finally, given the recent advances in computing, we discuss how machine learning methods can be used to accelerate drug discovery efforts.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"46 5","pages":"453-467"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983283","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}
引用次数: 0
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