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Trop2 immunoPET/CT in clinical practice: facts and challenges Trop2免疫pet /CT在临床实践中的应用：事实与挑战。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-26 DOI: 10.1016/j.drudis.2026.104684
Ailin Deng, Wenzhi Jia, Gang Huang, Jianjun Liu, Weijun Wei
{"title":"Trop2 immunoPET/CT in clinical practice: facts and challenges","authors":"Ailin Deng,&nbsp;Wenzhi Jia,&nbsp;Gang Huang,&nbsp;Jianjun Liu,&nbsp;Weijun Wei","doi":"10.1016/j.drudis.2026.104684","DOIUrl":"10.1016/j.drudis.2026.104684","url":null,"abstract":"<div><div>Trop2 (Trophoblast cell surface antigen 2) is a crucial tumor-associated antigen that is overexpressed in various epithelial-derived cancers. Thus, it has become a key target for molecular imaging and therapy. Immuno-positron emission tomography/computed tomography (immunoPET/CT), which combines the high specificity of antibody-based tracers with the high resolution of PET/CT, provides a new approach for noninvasive target visualization, accurate cancer diagnosis, staging, restaging, patient selection, and response monitoring in clinical cancer management. This review covers the design of tracers, preclinical progress, and translational applications of Trop2-targeted immunoPET/CT, highlighting its role in Trop2-specific cancer diagnosis and patient stratification, as well as its potential to guide and improve Trop2-targeted therapies. We also discuss current challenges and future directions for development, including the integration of multimodal imaging with personalized medicine. Trop2-targeted immunoPET/CT has significant potential to transform clinical practice and to improve precision oncology when combined with Trop2-targeted therapies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104684"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758566","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
Evolution of the division of labor for First-in-Class Drugs: A Quantitative Analysis of Trends across Company Types, Modalities, and Therapeutic Areas (2012–2024) 第一类药物的劳动分工演变：跨公司类型、模式和治疗领域趋势的定量分析（2012-2024）。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-15 DOI: 10.1016/j.drudis.2026.104669
Yusuke Izumiya , Yoshiyuki Kobayashi , Itsuki Kageyama , Shintaro Sengoku , Kota Kodama
{"title":"Evolution of the division of labor for First-in-Class Drugs: A Quantitative Analysis of Trends across Company Types, Modalities, and Therapeutic Areas (2012–2024)","authors":"Yusuke Izumiya ,&nbsp;Yoshiyuki Kobayashi ,&nbsp;Itsuki Kageyama ,&nbsp;Shintaro Sengoku ,&nbsp;Kota Kodama","doi":"10.1016/j.drudis.2026.104669","DOIUrl":"10.1016/j.drudis.2026.104669","url":null,"abstract":"<div><div>The pharmaceutical industry is transitioning toward diverse modalities, a shift that fundamentally reshapes the division of labor within R&amp;D. Analysis of 260 first-in-class drugs approved by the United States Food and Drug Administration (FDA; 2012–2024) reveals a steady increase in new modalities. Small- to medium-sized enterprises and spin-offs are identified as primary originators. Conversely, large pharma serve as development and commercialization partners, sourcing most new modality pipelines externally. Spin-offs may serve as translational vehicles for transitioning frontier science into clinical assets. This collaborative model prioritizes unmet medical needs, consistent with significantly higher rates of access to FDA-expedited approval programs for new modalities compared with conventional ones.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104669"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715460","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
Targeting S1P signaling for drug development 靶向S1P信号用于药物开发。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-16 DOI: 10.1016/j.drudis.2026.104674
Yaru Liu , Yali Song , Youzhi Wang , Jinxin Wang , Kan Yang
{"title":"Targeting S1P signaling for drug development","authors":"Yaru Liu ,&nbsp;Yali Song ,&nbsp;Youzhi Wang ,&nbsp;Jinxin Wang ,&nbsp;Kan Yang","doi":"10.1016/j.drudis.2026.104674","DOIUrl":"10.1016/j.drudis.2026.104674","url":null,"abstract":"<div><div>Sphingosine-1-phosphate (S1P), a downstream metabolite of the sphingolipid pathway, exerts diverse biological functions, is implicated in a wide spectrum of diseases, and has been shown to have central roles in regulating cell proliferation, migration, and immune cell trafficking. Five agonists of its receptor have been approved for the treatment of multiple sclerosis, and an inhibitor targeting its production is currently undergoing clinical trials for cancer therapy. Here, we discuss the modulators and their preliminary structure–activity relationships in terms of the generation, transportation, and degradation of S1P.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104674"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715426","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
New perspectives for better R&D performance: lessons learned from leading pharma companies 提高研发绩效的新视角：从领先制药公司吸取的经验教训。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-17 DOI: 10.1016/j.drudis.2026.104677
Alexander Schuhmacher , Oliver Gassmann , Sara Knapp , Dominik Hartl , Markus Hinder
{"title":"New perspectives for better R&D performance: lessons learned from leading pharma companies","authors":"Alexander Schuhmacher ,&nbsp;Oliver Gassmann ,&nbsp;Sara Knapp ,&nbsp;Dominik Hartl ,&nbsp;Markus Hinder","doi":"10.1016/j.drudis.2026.104677","DOIUrl":"10.1016/j.drudis.2026.104677","url":null,"abstract":"<div><div>The research and development (R&amp;D) productivity of pharmaceutical companies has been widely studied and analyzed for many years in both academia and industry, and pharmaceutical companies have launched various initiatives to improve their R&amp;D efficiency, such as by opening R&amp;D toward external innovation, improved decision-making, or better clinical trial management. However, these efforts are based primarily on an inward-looking organizational perspective and have so far not benchmarked new drugs invented internally and those acquired from external sources. Here, we analyze new drugs approved between 2011 and 2022 developed by the top 20 pharmaceutical companies, differentiating between internal and external innovation, with a particular focus on internally invented new drugs. Based on our analysis, we provide deep insights into the R&amp;D strategies of the leading companies and draw conclusions about how companies could further improve their R&amp;D performance.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104677"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721076","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
Medicinal chemistry strategies to breach the blood–brain barrier: structural design principles for brain-targeted therapeutics 突破血脑屏障的药物化学策略：脑靶向治疗的结构设计原则。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-16 DOI: 10.1016/j.drudis.2026.104673
Harikesh Kumar Gupta, Jatin Jangra, Vishwakarma Krishna Ramesh, Isha Mahindru, Rajnish Kumar
{"title":"Medicinal chemistry strategies to breach the blood–brain barrier: structural design principles for brain-targeted therapeutics","authors":"Harikesh Kumar Gupta,&nbsp;Jatin Jangra,&nbsp;Vishwakarma Krishna Ramesh,&nbsp;Isha Mahindru,&nbsp;Rajnish Kumar","doi":"10.1016/j.drudis.2026.104673","DOIUrl":"10.1016/j.drudis.2026.104673","url":null,"abstract":"<div><div>The blood–brain barrier (BBB) remains a critical limitation in central nervous system (CNS) drug development, restricting brain exposure to most therapeutics. Despite advances in macromolecular delivery, small molecules continue to predominate, necessitating the rational optimization of BBB permeability. This review integrates recent medicinal chemistry strategies focused on fine-tuning key physicochemical parameters, including lipophilicity, p<em>K</em><sub>a</sub>, molecular weight, hydrogen bond donors, rotatable bonds and topological polar surface area, which govern passive diffusion and brain penetration. Structural modifications such as fluorination, bioisosteric replacement, intramolecular hydrogen bond masking and prodrug approaches are discussed alongside strategies to mitigate efflux and exploit carrier-mediated transport. The integration of <em>in silico</em> tools and experimental models provides a cohesive framework for designing next-generation CNS therapeutics with optimized permeability and efficacy profiles.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104673"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715453","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
Physics-inspired explainable AI for mechanistic and decision support in drug discovery 受物理启发的可解释AI，用于药物发现的机制和决策支持。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-21 DOI: 10.1016/j.drudis.2026.104679
Antonio Lavecchia
{"title":"Physics-inspired explainable AI for mechanistic and decision support in drug discovery","authors":"Antonio Lavecchia","doi":"10.1016/j.drudis.2026.104679","DOIUrl":"10.1016/j.drudis.2026.104679","url":null,"abstract":"<div><div>Explainable artificial intelligence (XAI) is increasingly recognized as essential for trustworthy drug discovery, yet many approaches remain post hoc and correlational. This review examines physics-inspired XAI as a framework for improving mechanistic interpretability and decision support at the molecular design stage. We highlight its strengths in modeling molecular recognition and local structure–property relations, while emphasizing that efficacy and toxicity emerge from biological and pharmacological processes beyond molecular physics. Current evidence suggests that explainability improves prioritization and experimental efficiency, although its impact on overall R&amp;D outcomes remains limited. We propose ‘Molecular Intelligence’ as a decision-centric framework integrating prediction, validation and domain knowledge.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104679"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758572","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
Usefulness of the sulfonamide motif in medicinal chemistry: exploring the pharmacological landscape of FDA-approved and investigational sulfonamide drugs 磺胺基序在药物化学中的用途：探索fda批准和正在研究的磺胺类药物的药理学景观。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-20 DOI: 10.1016/j.drudis.2026.104675
Sébastien Sueron , Alban Vigroux , François-Hugues Porée
{"title":"Usefulness of the sulfonamide motif in medicinal chemistry: exploring the pharmacological landscape of FDA-approved and investigational sulfonamide drugs","authors":"Sébastien Sueron ,&nbsp;Alban Vigroux ,&nbsp;François-Hugues Porée","doi":"10.1016/j.drudis.2026.104675","DOIUrl":"10.1016/j.drudis.2026.104675","url":null,"abstract":"<div><div>The sulfonamide motif is widely used in the design of small molecules owing to its enzymatic stability but also its potentiality to improve target engagement and to provide a beneficial ADME profile. From the commercialization of Prontosil® in 1933 until 2023, a total of 91 compounds containing a sulfonamide moiety have received approval from the FDA. In parallel, analysis of the ChEMBl database revealed that 200 sulfonamide-containing compounds have entered clinical trials between 1998 and 2023. This review aims to present an exhaustive assessment of the sulfonamide motif in approved and investigational drugs, encompassing its pharmacokinetic and pharmacological properties, physicochemical properties, biological targets and temporal trends. Our analysis reveals a shift from traditional applications in antibacterials and diuretics toward modern oncology and antiviral therapeutics, with investigational compounds increasingly targeting GPCRs and kinases. Using selected case studies of approved drugs, we demonstrate that sulfonamide incorporation can enhance biological activity and modulate drug-like properties, providing evidence-based guidance to medicinal chemists.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104675"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758578","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
The host–steroid–microbiome axis: Microbial remodeling of steroid scaffolds and its implications for metabolic and endocrine disorders 宿主-类固醇-微生物组轴：类固醇支架的微生物重塑及其对代谢和内分泌紊乱的影响。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-26 DOI: 10.1016/j.drudis.2026.104683
Thanga Yogeshwaran Gajendran , Nila Ganamurali , Sarvesh Sabarathinam
{"title":"The host–steroid–microbiome axis: Microbial remodeling of steroid scaffolds and its implications for metabolic and endocrine disorders","authors":"Thanga Yogeshwaran Gajendran ,&nbsp;Nila Ganamurali ,&nbsp;Sarvesh Sabarathinam","doi":"10.1016/j.drudis.2026.104683","DOIUrl":"10.1016/j.drudis.2026.104683","url":null,"abstract":"<div><div>Steroids, chemically conserved yet functionally diverse, integrate metabolic, endocrine and microbial networks. Beyond host hormones acting via specific receptors, the gut microbiome edits steroid scaffolds, yielding metabolites that reshape systemic signaling. We introduce the host–steroid–microbiome axis, framing steroids as holobiont currencies coordinating metabolism, immunity and endocrine balance. This continuum links endogenous steroidogenesis, microbial transformations (via hydroxysteroid dehydrogenases, sulfatases and β-glucuronidases) and host receptor modulation (farnesoid X, Takeda G protein-coupled receptor 5 (TGR5), estrogen, androgen and glucocorticoid receptors), impacting bile acid signaling, glucose/lipid metabolism and hormone-related diseases. Steroidomics, multiomics, Cryogenic electron microscopy (cryo-EM), artificial intelligence (AI) modeling and digital twins illuminate these interactions, enabling precision endocrinology informed by the microbiome, diet and genetics. A roadmap unites microbial ecology, steroid chemistry and AI for therapeutic targeting.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104683"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758607","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
The FATP2 axis in cancer: Structural informatics and implications for drug discovery 癌症中的FATP2轴：结构信息学和药物发现的意义。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-04-22 DOI: 10.1016/j.drudis.2026.104680
Yuanyuan Wang , Yunjiao Zhang , Bo Zhang , Faez Iqbal Khan
{"title":"The FATP2 axis in cancer: Structural informatics and implications for drug discovery","authors":"Yuanyuan Wang ,&nbsp;Yunjiao Zhang ,&nbsp;Bo Zhang ,&nbsp;Faez Iqbal Khan","doi":"10.1016/j.drudis.2026.104680","DOIUrl":"10.1016/j.drudis.2026.104680","url":null,"abstract":"<div><div>Dysregulated fatty acid (FA) metabolism sustains tumour growth and metastasis, yet effective therapeutic interventions remain elusive. Fatty acid transport protein 2 (FATP2/<em>SLC27A2</em>) has emerged as a pivotal metabolic gatekeeper, coordinating the uptake and activation of long-chain fatty acids (LCFAs). Despite its established role in driving tumour-associated immune suppression and metabolic dependencies, FATP2-directed drug discovery is limited by the lack of high-resolution structural information. This review integrates recent biological insights with computational and structural informatics, assessing reported chemotypes against available homology and AlphaFold-derived models to propose a rational, structure-based framework for next-generation FATP2 inhibitor design and prioritization.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104680"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758600","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
AI agents in drug discovery: applications and case studies 药物发现中的人工智能代理：应用和案例研究。
IF 7.5 2区 医学
Drug Discovery Today Pub Date : 2026-05-01 Epub Date: 2026-03-24 DOI: 10.1016/j.drudis.2026.104650
Dinh Long Huynh , Srijit Seal
{"title":"AI agents in drug discovery: applications and case studies","authors":"Dinh Long Huynh ,&nbsp;Srijit Seal","doi":"10.1016/j.drudis.2026.104650","DOIUrl":"10.1016/j.drudis.2026.104650","url":null,"abstract":"<div><div>AI agents are emerging as transformative tools in drug discovery, with the ability to autonomously reason, act and learn through complicated research workflows. Building on large language models and specialized tools, these systems can integrate biomedical data, execute tasks, conduct experiments and iteratively refine hypotheses. We provide a conceptual overview of agentic AI architectures and illustrate their applications across key stages of drug discovery, including literature synthesis, automated protocol generation, toxicity prediction, small-molecule synthesis, drug repurposing and end-to-end decision-making. Early implementations demonstrate substantial gains in speed, reproducibility and scalability. We discuss the challenges related to data heterogeneity, system reliability, privacy, benchmarking and outline future directions toward technology in support of science and translation.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 3","pages":"Article 104650"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519356","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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