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GPR17 - orphan G protein-coupled receptor with therapeutic potential. GPR17 -孤儿G蛋白偶联受体，具有治疗潜力。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-20 DOI: 10.1016/j.tips.2025.05.001
Michael Lewash, Evi Kostenis, Christa E Müller
{"title":"GPR17 - orphan G protein-coupled receptor with therapeutic potential.","authors":"Michael Lewash, Evi Kostenis, Christa E Müller","doi":"10.1016/j.tips.2025.05.001","DOIUrl":"10.1016/j.tips.2025.05.001","url":null,"abstract":"<p><p>The orphan G protein-coupled receptor (GPCR) GPR17, whose physiological agonist remains unknown, has emerged as a promising drug target for multiple sclerosis (MS). Blockade of the receptor enables remyelination and may offer a novel therapeutic strategy for MS. Only recently, potent and selective tool compounds for GPR17 have become available, and patents on antagonists have surged, leading to the first clinical candidate, the GPR17 antagonist PTD802, which is to be developed for MS therapy. This may pave the way for further clinical studies exploring additional indications, such as neurodegenerative diseases. The newly determined cryo-electron microscopy (cryo-EM) structure of GPR17 is expected to facilitate future structure-based drug design efforts. This review presents and discusses these latest developments, providing a timely and comprehensive overview to guide future research in the field.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340425","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
Protein acylations in cancer immunity: effects and therapeutic opportunities. 蛋白质酰化在癌症免疫中的作用和治疗机会。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-19 DOI: 10.1016/j.tips.2025.05.011
Jia-Cheng Lai, Yi-Ting Jiang, Shougeng Liu, Simeng Wang, Wei Cui, Lihui Wang
{"title":"Protein acylations in cancer immunity: effects and therapeutic opportunities.","authors":"Jia-Cheng Lai, Yi-Ting Jiang, Shougeng Liu, Simeng Wang, Wei Cui, Lihui Wang","doi":"10.1016/j.tips.2025.05.011","DOIUrl":"10.1016/j.tips.2025.05.011","url":null,"abstract":"<p><p>Acylations are conserved and dynamic modifications that control various biological processes, including gene transcription and protein biology, and have been tied to diseases, such as cancers. Due to their reversible characteristic, acylations exhibit great therapeutic potential through targeting of their regulatory enzymes and proteins. Recent studies have improved our understanding of the close interplay between acylations and the tumor immune microenvironment (TIME), showing the potential to improve antitumor immune responses via acylation manipulation. Herein, we review the effects of acylations, including acetylation, lactylation, palmitoylation, and some less well-known acylations on cancer immunity, and corresponding therapeutic opportunities. Specifically, we bring into focus diverse roles of different acylation-related enzymes, metabolites, or substrates to provide insights into targeting acylations to increase antitumor immunity and generate broader research enthusiasm.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337035","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
Anti-remodeling therapies in pulmonary arterial hypertension. 肺动脉高压的抗重塑治疗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-19 DOI: 10.1016/j.tips.2025.05.004
Olivier Boucherat, Sébastien Bonnet, Steeve Provencher, François Potus
{"title":"Anti-remodeling therapies in pulmonary arterial hypertension.","authors":"Olivier Boucherat, Sébastien Bonnet, Steeve Provencher, François Potus","doi":"10.1016/j.tips.2025.05.004","DOIUrl":"10.1016/j.tips.2025.05.004","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a progressive, life-threatening vasculopathy characterized by sustained vasoconstriction and pathological remodeling of small pulmonary arteries. While current vasodilator therapies improve symptoms and survival, they are not curative and fail to reverse vascular remodeling. Recently, a shift toward disease-modifying strategies has emerged, driven by preclinical advances now entering clinical translation. The approval of sotatercept, the first agent presumed to target vascular remodeling, and the development of seralutinib, an inhaled tyrosine kinase inhibitor (TKI), mark key milestones. In this review, we focus on anti-remodeling therapies that have progressed from preclinical models to clinical trials. These include agents targeting cell cycle regulators, kinase pathways, epigenetic modifiers, bone morphogenetic protein receptor type 2 (BMPR2) signaling, and senescence in pulmonary arterial smooth muscle cells (PASMCs), offering renewed hope for durable PAH treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337034","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 plasma membrane cholesterol as a novel anticancer therapy. 靶向质膜胆固醇作为一种新的抗癌疗法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-19 DOI: 10.1016/j.tips.2025.06.001
Alfredo Erazo-Oliveras, Mónica Muñoz-Vega, Robert S Chapkin
{"title":"Targeting plasma membrane cholesterol as a novel anticancer therapy.","authors":"Alfredo Erazo-Oliveras, Mónica Muñoz-Vega, Robert S Chapkin","doi":"10.1016/j.tips.2025.06.001","DOIUrl":"10.1016/j.tips.2025.06.001","url":null,"abstract":"<p><p>An effective therapeutic strategy to treat oncogenic Wnt signaling in the context of colorectal cancer (CRC) remains elusive. A new study from Cho and colleagues describes a novel mechanistic link between the loss of canonical adenomatous polyposis coli (APC) function, membrane cholesterol, and an innovative drug target to specifically suppress the cholesterol-Dvl-β-catenin signaling axis.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337036","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
Mining microbial metabolites of GPCR-targeted drugs. 挖掘gpcr靶向药物的微生物代谢物。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-18 DOI: 10.1016/j.tips.2025.05.014
Chen Zhang, Peter J Turnbaugh
{"title":"Mining microbial metabolites of GPCR-targeted drugs.","authors":"Chen Zhang, Peter J Turnbaugh","doi":"10.1016/j.tips.2025.05.014","DOIUrl":"10.1016/j.tips.2025.05.014","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are a large superfamily of receptors critical for mammalian cell-cell communication and a common drug target. A new study has revealed that the human gut microbiome can metabolize GPCR-targeted drugs into both expected and surprising metabolites, with potentially broad implications for the treatment of disease.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333930","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
Bright sorting yields drug-like anti-amyloid antibodies. 明亮分选产生类似药物的抗淀粉样抗体。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-16 DOI: 10.1016/j.tips.2025.05.013
Bingqian Li, Pietro Sormanni
{"title":"Bright sorting yields drug-like anti-amyloid antibodies.","authors":"Bingqian Li, Pietro Sormanni","doi":"10.1016/j.tips.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.tips.2025.05.013","url":null,"abstract":"<p><p>Conformation-specific antibodies represent powerful tools for targeting pathogenic amyloid aggregates. However, the discovery of aggregate-selective antibodies with drug-like developability properties has been slow, inefficient, and difficult to generalise across different amyloid targets. The Tessier lab has developed a yeast-display screening pipeline that enables conformation-specific antibody discovery against diverse aggregated proteins.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317968","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
Fluorescent RNAs: new opportunities for drug discovery. 荧光rna：药物发现的新机遇。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-14 DOI: 10.1016/j.tips.2025.05.006
Fangting Zuo, Ziheng Gao, Xianjun Chen, Yi Yang
{"title":"Fluorescent RNAs: new opportunities for drug discovery.","authors":"Fangting Zuo, Ziheng Gao, Xianjun Chen, Yi Yang","doi":"10.1016/j.tips.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.tips.2025.05.006","url":null,"abstract":"<p><p>Fluorescent RNAs (FRs), RNA mimics of fluorescent proteins (FPs), have emerged as a promising approach for tagging RNAs and investigating their complex spatiotemporal dynamics and biological functions. Moreover, FR-derived biosensors (FRBs) also provide useful tools for point-of-care testing of a wide range of targets, from small molecules, nucleic acids, and proteins to various pathogens. However, it is still unclear whether and how FRs and FRBs can be used to accelerate drug discovery. In this review article, we briefly summarize the recent advances in FRs and FRBs and focus on recent works showing how FRs and FRBs can be used during different stages of RNA and small-molecule drug discovery. Furthermore, we discuss limitations of current technologies and potential pathways for moving forward.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294969","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
Exploring new frontiers in LAG-3 biology and therapeutics. 探索LAG-3生物学和治疗学的新领域。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-12 DOI: 10.1016/j.tips.2025.05.008
Jun Wang, Christian Klein, Jennifer R Cochran, Jonathan Sockolosky, Shaun M Lippow
{"title":"Exploring new frontiers in LAG-3 biology and therapeutics.","authors":"Jun Wang, Christian Klein, Jennifer R Cochran, Jonathan Sockolosky, Shaun M Lippow","doi":"10.1016/j.tips.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.tips.2025.05.008","url":null,"abstract":"<p><p>Lymphocyte activation gene-3 (LAG-3) has emerged as a critical immune checkpoint receptor primarily modulating T-cell responses through distinct immune regulatory mechanisms. Recent advances have elucidated LAG-3's complex receptor-ligand interactions, structure-function relationships, and unique signaling pathways. LAG-3 antagonistic antibodies, such as relatlimab approved for melanoma, have shown promising efficacy with favorable toxicity profiles, though only in combinational therapies. While LAG-3's role in oncology continues to expand, it is also gaining recognition as a potential therapeutic target for other disorders. This review highlights recent progress in understanding LAG-3's molecular features, ligand regulation, signaling, and immune modulation mechanisms. Additionally, it explores emerging questions in oncology and the exciting potential of therapies targeting the LAG-3 pathway in autoimmune disease. A deeper understanding of LAG-3's confounding biology and disease relevance would drive the development of novel immunotherapies across broader clinical indications.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294968","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
At last: the mitochondrial pyruvate carrier structure revealed! 最终：线粒体丙酮酸载体结构揭示！
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-10 DOI: 10.1016/j.tips.2025.05.010
Brian N Finck, Christy M Hadfield, Kyle S McCommis
{"title":"At last: the mitochondrial pyruvate carrier structure revealed!","authors":"Brian N Finck, Christy M Hadfield, Kyle S McCommis","doi":"10.1016/j.tips.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.tips.2025.05.010","url":null,"abstract":"<p><p>Mitochondrial pyruvate carrier (MPC) inhibitors have shown promise as therapeutics for treating several chronic diseases. However, the structure of MPC and the molecular mechanisms by which it interacts with inhibitors have remained unclear, impeding rational drug design. Multiple groups have now independently resolved the structure of the MPC heterodimer.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276003","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
Optogenetic engineering for precision cancer immunotherapy. 精准癌症免疫治疗的光基因工程。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-10 DOI: 10.1016/j.tips.2025.05.002
Yuepeng Ke, Siyao Liu, Yun Huang, Tien-Hung Lan, Yubin Zhou
{"title":"Optogenetic engineering for precision cancer immunotherapy.","authors":"Yuepeng Ke, Siyao Liu, Yun Huang, Tien-Hung Lan, Yubin Zhou","doi":"10.1016/j.tips.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.tips.2025.05.002","url":null,"abstract":"<p><p>Cancer immunotherapy has revolutionized oncology, but its full potential remains constrained by treatment resistance, limited durability, immune evasion, and systemic toxicity. Overcoming these obstacles requires innovative strategies for remote and targeted immunomodulation. Opsin-free optogenetics has emerged as a powerful tool in cancer immunotherapy because its versatility and photoactivation kinetics align with the timescale of immune cell signaling, and it has given rise to the subfield of optogenetic immunoengineering. This review explores design strategies and key applications of optogenetic immunoengineering, focusing on the opsin-free optogenetic toolkit in immunotherapy and its ability to modulate the cancer-immunity cycle which is required for amplifying and sustaining antitumor responses. By enabling precise regulation of both innate and adaptive immunity, as demonstrated in recent preclinical studies, optogenetic immunoengineering holds great promise for advancing next-generation precision medicine.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276004","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
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