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Harnessing zebrafish as a model for photopharmacology: Insights into light-controlled biological effects of photoswitchable drugs 利用斑马鱼作为光药理学的模型：对光转换药物的光控生物效应的见解。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104477
Guilherme Pietro da Silva , Janine Doorduin , Wiktor Szymanski , Rosane Souza da Silva , Philip Elsinga , Carla Denise Bonan
{"title":"Harnessing zebrafish as a model for photopharmacology: Insights into light-controlled biological effects of photoswitchable drugs","authors":"Guilherme Pietro da Silva ,&nbsp;Janine Doorduin ,&nbsp;Wiktor Szymanski ,&nbsp;Rosane Souza da Silva ,&nbsp;Philip Elsinga ,&nbsp;Carla Denise Bonan","doi":"10.1016/j.drudis.2025.104477","DOIUrl":"10.1016/j.drudis.2025.104477","url":null,"abstract":"<div><div>Photopharmacology is an emerging field of pharmacological sciences that enables precise spatiotemporal control over drug activation with light. In its reversible mode, it relies on photoswitchable bioactive compounds. The capacity to reversibly activate and deactivate drugs derivatized with photoswitches enables us to avoid side effects and environmental toxicity. Zebrafish represent an emerging and privileged model for translational photopharmacology because of their optical transparency at early developmental stages, genetic tractability, and well-characterized biological mechanisms. In this review, we discuss the use of zebrafish in advancing photopharmacology and understanding the effects of light-controlled interventions using photoswitchable bioactive compounds.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 10","pages":"Article 104477"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
RNA virus and DNA virus initiations of autoimmune diseases and/or dementias 自身免疫性疾病和/或痴呆的RNA病毒和DNA病毒启动。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104481
Kevin Roe
{"title":"RNA virus and DNA virus initiations of autoimmune diseases and/or dementias","authors":"Kevin Roe","doi":"10.1016/j.drudis.2025.104481","DOIUrl":"10.1016/j.drudis.2025.104481","url":null,"abstract":"<div><div>There are viral pathogen pathways to initiate autoimmune diseases, such as multiple sclerosis, directly or indirectly, by reactivating latent viruses including human herpesviruses. After initial infections, these DNA viruses can enter latency but periodically reactivate into active infections following triggers: medical treatments inducing immunosuppressions; and infections by immunosuppressive pathogens including RNA viruses, stress or malnutrition. An indirect causation pathway for autoimmune diseases can utilize immune suppressions by RNA virus infections, which trigger reactivation of latent herpesviruses capable of directly causing autoimmune diseases. Although it is believed that general inflammation, not specific pathogens, causes autoimmune diseases, experimental evidence indicates autoimmune diseases are caused by herpesvirus reactivations. Such viral reactivations can be induced by immunosuppressions during severe pathogen infections, particularly by RNA virus infections.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 11","pages":"Article 104481"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
DILIrank 2.0: An updated and expanded database for drug-induced liver injury risk based on FDA labeling and a literature review. DILIrank 2.0：一个更新和扩展的基于FDA标签和文献综述的药物性肝损伤风险数据库。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104485
AyoOluwa O Olubamiwa, Yanyan Qu, Skylar Connor, Weida Tong, Dongying Li, Minjun Chen
{"title":"DILIrank 2.0: An updated and expanded database for drug-induced liver injury risk based on FDA labeling and a literature review.","authors":"AyoOluwa O Olubamiwa, Yanyan Qu, Skylar Connor, Weida Tong, Dongying Li, Minjun Chen","doi":"10.1016/j.drudis.2025.104485","DOIUrl":"10.1016/j.drudis.2025.104485","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is of great concern in drug development and public health. DILIrank 1.0, a widely used public dataset that ranks FDA-approved drugs by their potential to cause DILI, has significantly enabled the development of new methods for improved DILI assessment. Here, we introduce DILIrank2.0, an essential update of DILIrank 1.0, to capture new non-biologics drug and liver-related adverse event data generated since its inception 15 years ago. Using DILIrank 2.0, we also observe changes in the DILI profiles of approved drugs following the introduction of different FDA regulatory programs. DILIrank 2.0 is an up-to-date resource that offers opportunities for supporting DILI safety assessment, predictive model development, and evaluation of new approach methods (NAMs).</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104485"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 glues as GPCR modulators: unveiling three distinct mechanistic pathways for signal regulation. 分子胶作为GPCR调节剂：揭示信号调节的三种不同的机制途径。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104484
Yuxuan Xing, Jianyang Ao, Xiaoli Zhu, Zhengjun Chai, Shaoyong Lu
{"title":"Molecular glues as GPCR modulators: unveiling three distinct mechanistic pathways for signal regulation.","authors":"Yuxuan Xing, Jianyang Ao, Xiaoli Zhu, Zhengjun Chai, Shaoyong Lu","doi":"10.1016/j.drudis.2025.104484","DOIUrl":"10.1016/j.drudis.2025.104484","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) constitute a large and pharmaceutically significant family of membrane proteins that mediate a wide range of physiological responses. Conventional modulation strategies primarily target orthosteric sites, but recent studies have identified a novel class of modulators known as 'molecular glues' that stabilize specific receptor-transducer interfaces. This review categorizes molecular glues into three mechanistic groups on the basis of their mode of action: those that directly stabilize receptor-transducer complexes, those that induce biased signaling through allosteric interactions, and those that modulate signaling indirectly by targeting allosteric regulatory sites. With advances in structural biology and computational methodologies, molecular glues are increasingly recognized as promising biased agonists, next-generation therapeutic agents, and valuable chemical tools for elucidating GPCR signaling pathways.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104484"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Challenges of broad-spectrum antiviral drug discovery and development for emerging pathogens. 新出现病原体的广谱抗病毒药物发现和开发的挑战。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104486
Holli-Joi Martin, Jon-Michael Beasley, Enes Kelestemur, Zoe Sessions, Stephan Ludwig, Nathaniel J Moorman, Ralph Baric, Eugene N Muratov, Alexander Tropsha
{"title":"Challenges of broad-spectrum antiviral drug discovery and development for emerging pathogens.","authors":"Holli-Joi Martin, Jon-Michael Beasley, Enes Kelestemur, Zoe Sessions, Stephan Ludwig, Nathaniel J Moorman, Ralph Baric, Eugene N Muratov, Alexander Tropsha","doi":"10.1016/j.drudis.2025.104486","DOIUrl":"10.1016/j.drudis.2025.104486","url":null,"abstract":"<p><p>Broad-spectrum antiviral agent (BSAA) drugs are essential in the fight against viral, especially emerging, diseases. However, their development faces several challenges including insufficiently focused funding, fragmented research efforts and limited systematic data on BSAAs. In this review, we highlight these challenges, summarize accessible collections of data on antiviral compounds and viral targets, and explore possible directions toward the development of BSAAs. Whereas most existing BSAAs have been discovered serendipitously, we posit that rational, and feasible, design of direct-acting BSAAs should be focused on homologous targets found in viruses within a single viral family.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104486"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
RXFP1, the relaxin receptor: Lost and found in translation. 松弛素受体RXFP1：在翻译中丢失和发现。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-23 DOI: 10.1016/j.drudis.2025.104483
Mark Lal, Sean Eddy, Anna Walentinsson, Jeffrey B Hodgin, Pernille B L Hansen, Magnus Althage, Matthias Kretzler
{"title":"RXFP1, the relaxin receptor: Lost and found in translation.","authors":"Mark Lal, Sean Eddy, Anna Walentinsson, Jeffrey B Hodgin, Pernille B L Hansen, Magnus Althage, Matthias Kretzler","doi":"10.1016/j.drudis.2025.104483","DOIUrl":"10.1016/j.drudis.2025.104483","url":null,"abstract":"<p><p>Relaxin, historically recognized as a pregnancy hormone, is today characterized as a circulating protein possessing several cardiovascular modulating and anti-fibrotic properties of high clinical interest. Although it has long been recognized that there exists remarkable species diversity regarding the tissue sources and physiological effects of relaxin, there is a considerable gap in our translational understanding of its signal transducing receptor, relaxin family peptide receptor 1 (RXFP1). Here, we review the topic and highlight the striking contrast in RXFP1 tissue expression from rodents to humans, and describe how a renewed focus on RXFP1 target pharmacology is critical to delivering future clinical success in relation to this physiologically important signaling receptor.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104483"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Methionine biosynthesis as a key metabolic pathway for antimicrobial drug discovery in Streptococcus mutans. 甲硫氨酸的生物合成是变形链球菌发现抗微生物药物的关键代谢途径。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-23 DOI: 10.1016/j.drudis.2025.104482
Kulsum Fatima, Syed A Ali, Asad U Khan
{"title":"Methionine biosynthesis as a key metabolic pathway for antimicrobial drug discovery in Streptococcus mutans.","authors":"Kulsum Fatima, Syed A Ali, Asad U Khan","doi":"10.1016/j.drudis.2025.104482","DOIUrl":"10.1016/j.drudis.2025.104482","url":null,"abstract":"<p><p>Streptococcus mutans, a Gram-positive, facultative anaerobic bacterium, is a key contributor to dental caries. It forms biofilms to colonize the tooth surface, has stress resistance mechanisms to survive the fluctuating oral environment, and produces virulence factors, all of which cause enamel demineralization, acid production, and caries development. Traditional antimicrobial strategies target central metabolic pathways in S. mutans, but most enzymes are conserved between humans and bacteria. However, one prospective approach is to target methionine biosynthesis. This pathway is essential for protein synthesis, methylation reactions, and oxidative stress resistance, supporting bacterial growth, biofilm formation, and cariogenic potential. Notably, its selective inhibition can be achieved because this pathway is absent in humans. Therefore, targeting enzymes of this pathway could halt bacterial growth and virulence, offering a novel antimicrobial strategy to treat S. mutans infections.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104482"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Rational discovery of molecular glue degraders based on block chemistry 基于块化学的分子胶水降解剂的合理发现。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-20 DOI: 10.1016/j.drudis.2025.104480
Junjie Wei , Wenjing Feng , Qingsong Chen , Qianbin Li , Zhuo Chen
{"title":"Rational discovery of molecular glue degraders based on block chemistry","authors":"Junjie Wei ,&nbsp;Wenjing Feng ,&nbsp;Qingsong Chen ,&nbsp;Qianbin Li ,&nbsp;Zhuo Chen","doi":"10.1016/j.drudis.2025.104480","DOIUrl":"10.1016/j.drudis.2025.104480","url":null,"abstract":"<div><div>Molecular glue degraders (MGDs) have emerged as promising therapeutic agents with substantial clinical potential and growing commercial interest in terms of their pharmaceutical development. Nevertheless, the translation of MGDs into clinical trials remains limited. Recent advances in drug discovery technologies are facilitating a paradigm shift in MGD development, from serendipitous discovery to rational design. Here, we systematically analyze rational MGD discovery strategies, focusing on E3 ligase and target ligand modifications. Furthermore, we highlight cutting-edge technologies and the latest trends in MGD development. Thus, this review provide valuable insights for researchers and could help accelerate the clinical translation of MGDs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 11","pages":"Article 104480"},"PeriodicalIF":7.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Evolutionary hallmark-inspired identification of prognostic biomarkers and drug targets for cancers 受进化标志启发的癌症预后生物标志物和药物靶点鉴定。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-18 DOI: 10.1016/j.drudis.2025.104479
Yang He, Chen-Wei Zhou, Zhi-Wen Zhang, Yuan Quan, Hong-Yu Zhang
{"title":"Evolutionary hallmark-inspired identification of prognostic biomarkers and drug targets for cancers","authors":"Yang He,&nbsp;Chen-Wei Zhou,&nbsp;Zhi-Wen Zhang,&nbsp;Yuan Quan,&nbsp;Hong-Yu Zhang","doi":"10.1016/j.drudis.2025.104479","DOIUrl":"10.1016/j.drudis.2025.104479","url":null,"abstract":"<div><div>Identifying prognostic biomarkers and drug targets is important for cancer treatment. Accumulating evidence indicates that cancer progression reflects the reactivation of ancestral cellular programs, with evolutionarily ancient genes exerting a pivotal influence on tumor development. These ancient genes are markedly enriched among clinically validated biomarkers and therapeutic targets, highlighting their essential contribution to cancer pathogenesis and therapeutic development. The transcriptome age index (TAI) provides a quantitative framework to characterize transcriptome evolutionary dynamics, with demonstrated prognostic relevance across multiple cancer types. This review underscores the value of the TAI in shaping an evolutionary perspective for biomarker discovery and drug target identification, and considers its potential to advance precision oncology and future therapeutic development.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 11","pages":"Article 104479"},"PeriodicalIF":7.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Indole therapeutics: Latest FDA updates, ongoing trials, and future directions 吲哚疗法：最新的FDA更新，正在进行的试验和未来的方向。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2025-09-15 DOI: 10.1016/j.drudis.2025.104471
Noor-ul-Huda Butt , Sultan Nacak Baytas
{"title":"Indole therapeutics: Latest FDA updates, ongoing trials, and future directions","authors":"Noor-ul-Huda Butt ,&nbsp;Sultan Nacak Baytas","doi":"10.1016/j.drudis.2025.104471","DOIUrl":"10.1016/j.drudis.2025.104471","url":null,"abstract":"<div><div>Indole-based compounds serve as versatile pharmacophores across anticancer, antiviral, neurological, antimicrobial, and metabolic therapies. This review systematically analyses FDA-approved, withdrawn, and investigational indole-containing drugs over the past decade, focusing on evolving clinical outcomes, regulatory decisions, and therapeutic repositioning. It explores the shift from cytotoxic to targeted anticancer agents, the rise of indole-based antivirals in response to the COVID-19 pandemic, and the expanding interest in neuroactive indoles, particularly psychedelic compounds. Additionally, it highlights the underrepresentation of indole-based antibiotics and outlines progress in epigenetic and metabolic modulators. Through a detailed evaluation of pharmacological classes, clinical trial data, and structural characteristics, this review presents a comprehensive framework to guide future optimization and multi-target development of indole scaffolds.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 10","pages":"Article 104471"},"PeriodicalIF":7.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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