Medicinal Research Reviews最新文献

{"title":"Front Cover Image, Volume 46, Issue 5","authors":"Christoph Selg,&nbsp;Wolfgang A. G. Sauerwein,&nbsp;Evamarie Hey-Hawkins","doi":"10.1002/med.70092","DOIUrl":"https://doi.org/10.1002/med.70092","url":null,"abstract":"<p>The cover image is based on the article <i>Quantification of ¹⁰B and ¹¹B in Biological Samples in Translational Science and Clinical Applications for Boron Neutron Capture Therapy (BNCT)</i> by Christoph Selg et al., https://doi.org/10.1002/med.70060.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148695933","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}

{"title":"Quantification of 10B and 11B in Biological Samples in Translational Science and Clinical Applications for Boron Neutron Capture Therapy (BNCT)","authors":"Christoph Selg,&nbsp;Wolfgang A. G. Sauerwein,&nbsp;Evamarie Hey-Hawkins","doi":"10.1002/med.70060","DOIUrl":"10.1002/med.70060","url":null,"abstract":"<p>Boron neutron capture therapy (BNCT) is a targeted radiotherapy that exploits the selective accumulation of the ¹⁰B isotope within tumors, followed by irradiation with low-energy neutrons to induce high linear energy transfer particles with short path lengths, resulting in localized tumor cell destruction while sparing surrounding healthy tissue. Achieving optimal therapeutic efficacy requires precise quantification of ¹⁰B and ¹¹B in biological samples such as blood, tissue, and cells to inform treatment planning, dosimetry, and patient selection. This review provides a comprehensive assessment of analytical methods for boron (isotope) determination in BNCT, covering neutron-based techniques, mass spectrometry, nuclear imaging, and spectroscopic and magnetic approaches. Each method is discussed in terms of analytical principles, sample preparation, sensitivity, isotopic specificity, invasiveness, real-time capability, infrastructure complexity, and clinical applicability. Particular emphasis is placed on spatially resolved and in vivo techniques, as well as emerging theranostic strategies that integrate boron delivery with multimodal imaging. Despite significant technological progress, the lack of widely available, real-time, non-invasive, and ¹⁰B-specific dosimetry remains a key limitation for routine clinical implementation. In particular, while positron emission tomography-based approaches such as 4-borono-2-[¹⁸F]fluoro-L-phenylalanine provide essential information on boron biodistribution for treatment planning, they reflect tracer-level pharmacokinetics and therefore offer indirect rather than absolute quantification of therapeutic boron concentrations. This review critically assesses current methodologies in the context of clinical readiness and outlines future directions to support the translation of BNCT from bench to bedside.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1362-1389"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947318","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}

{"title":"Exercise-Induced Exerkines: Multi-Nodal Suppression of the NLRP3 Inflammasome and Translational Potential","authors":"Huaiming Wang,&nbsp;Zongqiang Jin,&nbsp;Shijing Di,&nbsp;Hamid Alizadeh","doi":"10.1002/med.70063","DOIUrl":"10.1002/med.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic low-grade inflammation driven by persistent NLRP3 inflammasome activation is a unifying pathophysiological feature of most non-communicable diseases (NCDs). Whereas single-target pharmacological inhibitors exhibit limited breadth and durability, regular moderate-intensity exercise confers robust multi-system protection through a diverse network of exerkines. This narrative review synthesizes evidence that exercise-released myokines (irisin, Metrnl, context-reprogrammed IL-6), hepatokines/adipokines (FGF21, adropin, adiponectin), metabolites (lactate, β-hydroxybutyrate), microbiota-derived factors (SCFAs, betulinic acid), and extracellular vesicle (EV)-delivered non-coding RNAs converge on every regulatory node of the canonical NLRP3 inflammasome to achieve multi-nodal suppression that is currently unmatched by any single pharmacological approach based on available evidence. Acute high-intensity exercise transiently activates NLRP3 via canonical danger signals, whereas chronic moderate-intensity training (150–300 min·wk⁻¹, 60%–75% HRmax) induces profound basal suppression through NF-κB attenuation, mitochondrial protection, direct interference with NEK7-NLRP3 interaction and ASC oligomerization, post-transcriptional silencing, and enhanced autophagic clearance. These mechanisms are supported by preclinical structural data and human biomarker studies across cardiovascular, metabolic, neurodegenerative, and musculoskeletal disorders. We propose a precision exercise medicine framework integrating exerkine/genetic/microbiome profiling to minimize non-responders, together with emerging mimetics, RNA therapeutics, and synergistic pharmacology, to deliver scalable systems-level modification of NLRP3-driven metaflammation.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1455-1472"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148012721","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}

{"title":"Insights From Spatiality: Accelerating Pharmaceutical Research Using Mass Spectrometry Imaging","authors":"Yuchen Zou,&nbsp;Zhiye Yan,&nbsp;Weiwei Tang,&nbsp;Bin Li","doi":"10.1002/med.70061","DOIUrl":"10.1002/med.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Mass spectrometry imaging (MSI) has emerged as a transformative technology in pharmaceutical research, offering unprecedented capabilities to visualize drug distribution, metabolism, and target engagement in biological tissues. By combining the molecular specificity of mass spectrometry with spatial imaging resolution, this label-free approach enables simultaneous mapping of drugs, metabolites, and endogenous molecules across tissue sections, providing comprehensive insights into drug absorption, distribution, metabolism, excretion, and toxicity properties. Recent technical advances have dramatically enhanced MSI capabilities, achieving spatial resolutions down to the cellular level. The integration of tandem mass spectrometry, ion mobility separation, and dedicated data analysis tools powered by artificial intelligence has further expanded the analytical power of MSI, enabling robust molecular identification and pattern recognition in complex biological matrices. MSI applications span critical areas of drug development, from characterizing blood-brain barrier permeability and CNS drug distribution to mapping tumor microenvironment heterogeneity and evaluating anticancer drug penetration. This technology has proven invaluable for assessing drug disposition in the heart, liver, kidney, lung, as well as the gastrointestinal tract and skin. As drug research increasingly embraces multimodal approaches and single-cell analysis, MSI continues to evolve as an indispensable tool for understanding drug behavior in complex biological systems, ultimately accelerating drug development and reducing clinical failures.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1434-1454"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148012754","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}

{"title":"STING: An Attractive Target for Autoimmune and Inflammatory Diseases","authors":"Zhenjiao Yang,&nbsp;Xinqiao Liu,&nbsp;Jinhong Zhan,&nbsp;Mingliang Ma,&nbsp;Yuanxiang Wang","doi":"10.1002/med.70058","DOIUrl":"10.1002/med.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Stimulator of Interferon Genes (STING) is a transmembrane homodimer protein located in the endoplasmic reticulum membrane and plays an essential role in human innate immunity. Hyperactivation of STING has been found in many autoimmune and inflammatory diseases. Therefore, STING has been recognized as a promising target for the treatment of these diseases. Many efforts have been devoted to identifying STING inhibitors and degraders. However, development of STING drug candidates is still challenging and in its infancy, and no candidates have been advanced into clinical trials. In this perspective, we comprehensively summarize recent advances in the development of STING inhibitors and degraders and highlight their design strategies. We also discuss the challenges and opportunities of STING inhibition and expect to shed light on future STING drug discovery.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1330-1347"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925130","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}

{"title":"Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery","authors":"Jun-Jie Wang,&nbsp;Ya Gao,&nbsp;Xin-Qian Ji,&nbsp;Jia-Yi Yin,&nbsp;Meng-Zhi Zhang,&nbsp;Bo Wang,&nbsp;Hui-Min Liu,&nbsp;Siqi Feng,&nbsp;Ning Wang,&nbsp;Guo-Liang Lu,&nbsp;Yan Li,&nbsp;Piet Herdewijn,&nbsp;Yi-Chao Zheng,&nbsp;Peng Yan,&nbsp;Xing-Jie Dai","doi":"10.1002/med.70052","DOIUrl":"10.1002/med.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Histone deacetylases (HDACs) are key epigenetic regulators involved in a variety of cancers, rendering them attractive therapeutic targets. Although several HDAC inhibitors have achieved clinical success, challenges such as poor isoform selectivity, acquired resistance, and off-target toxicity limit their broader application. Proteolysis-targeting chimeras (PROTACs) represent an innovative therapeutic strategy that enables ubiquitin–proteasome–mediated degradation of HDACs. This approach enhances specificity, overcomes resistance mechanisms, including those resulting from point mutations or persistent target activity, and enables sustained suppression at low concentrations, owing to its catalytic and event-driven mode of action. This review summarizes the structural classification and biological functions of HDACs and surveys recent advances in the design of HDAC-directed PROTACs. Key emphasis is placed on rational warhead selection, linker optimization, and the strategic choice of E3 ligase recruiters to guide degradation efficiency and isoform specificity. Representative degraders are evaluated for their pharmacological characteristics and antitumor efficacy across diverse malignancies. Current challenges and future directions for the development of HDAC degraders as clinically viable agents are also discussed.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1257-1278"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831596","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}

{"title":"Decoding WDR5-Mediated Interactions in Gliomas: Implications for Targeted Therapy","authors":"Edmund Jung,&nbsp;Christina Piperi","doi":"10.1002/med.70059","DOIUrl":"10.1002/med.70059","url":null,"abstract":"<p>Gliomas are aggressive and treatment-resistant tumors of the central nervous system, characterized by molecular heterogeneity, diffuse infiltration, rapid progression, and persistent poor prognosis despite multimodal therapy. Emerging evidence highlights the role of complex genetic changes (such as IDH1 and H3F3A mutations) and epigenetic interactions in reshaping chromatin structure and activity in gliomas, increasing their reliance on epigenetic regulators for their growth and resistance. The nuclear scaffolding protein WD repeat domain 5 (WDR5), is a core component of the MLL/SET1 (WRAD) methyltransferase complex, which has been recently validated as a molecular target for cancer. WDR5 implication in H3K4 trimethylation (H3K4me3)-mediated gene regulation sustains transcriptional programs linked to proliferation, ribosome biogenesis, stemness, and MYC-driven oncogenic activity. In gliomas, WDR5 expression is increased, promoting proliferation and migration, as well as maintaining the glioma stem cell population, contributing to tumor progression. Targeting of WDR5 through specific WIN-site and WBM-site inhibitors or PROTAC degraders has been shown to impair WRAD assembly, reduce H3K4me3 levels, weaken <i>MYC</i>-associated transcription, and suppress tumor growth. In this review, we highlight the significant role of WDR5 in gliomas as part of a tumor-specific epigenetic vulnerability network, providing a critical update on the major WDR5-targeted inhibitors and degraders for future therapeutic applications.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1348-1361"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925124","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}

{"title":"Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery","authors":"Lihua Liu,&nbsp;Minghui Yu,&nbsp;Xinnan Li,&nbsp;Jinyi Xu,&nbsp;Shaowen Xie,&nbsp;Shengtao Xu,&nbsp;Hong Yao","doi":"10.1002/med.70056","DOIUrl":"10.1002/med.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>The caseinolytic protease P (ClpP) is a conserved serine protease that functions with ATPases associated with diverse cellular activities (AAA+) chaperones to ensure protein quality control in organisms ranging from bacteria to human mitochondria. Its tetradecameric structure and adjustable gating support selective substrate recognition, unfolding, and proteolysis, thereby contributing to proteostasis, metabolic balance, stress responses, and bacterial virulence. Growing insights into human ClpP and ClpX complex (hClpXP) have further underscored its relevance to human disease. This review summarizes current knowledge of ClpP architecture and regulatory mechanisms, with emphasis on its roles in cellular homeostasis and pathophysiology. We highlight advances in small-molecule ClpP modulators, including activators, inhibitors, and emerging heterobifunctional degraders such as bacterial proteolysis-targeting chimeras (BacPROTACs) and mitochondrial-targeted PROTACs (MtPTACs), which harness ClpP activity for targeted protein degradation in antibacterial and anticancer applications. Despite notable progress, challenges remain, particularly in achieving selectivity between bacterial and human ClpP (hClpP), minimizing off-target effects, and preventing resistance. Future opportunities include designing reversible covalent inhibitors, developing novel allosteric modulators, and optimizing degrader architectures to expand therapeutic potential. ClpP-directed therapeutic strategies therefore represent a promising avenue for next-generation antibacterial and anticancer drug discovery.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1390-1433"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979711","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}

{"title":"Designing the Next Generation of Antibiotics: Structure, SAR, and Strategy in Medicinal Chemistry (2000–2025)","authors":"Ahmed A. Al-Karmalawy,&nbsp;Abdullah Al-Dakhil,&nbsp;Nada A. Ashour,&nbsp;Tarek A. Yousef,&nbsp;Samar S. Mabrouk,&nbsp;Arwa Omar Al Khatib,&nbsp;Samia S. Hawas","doi":"10.1002/med.70053","DOIUrl":"10.1002/med.70053","url":null,"abstract":"<div>\u0000 \u0000 <p>Antibacterial agents remain vital for managing infectious diseases, yet the global escalation of antimicrobial resistance (AMR) continues to compromise their therapeutic effectiveness. Despite decades of discovery and chemical refinement, most recently developed antibacterials belong to existing structural classes, underscoring a pressing need for innovative molecular scaffolds and mechanisms of action. This review provides a comprehensive medicinal-chemistry overview of major antibacterial classes, including β-lactams, glycopeptides, tetracyclines, fluoroquinolones, macrolides, aminoglycosides, oxazolidinones, polymyxins, and lipopeptides. The discussion emphasizes their structural frameworks, key structure–activity relationship (SAR) features, and the chemical strategies used to enhance potency, spectrum, and pharmacokinetic properties while counteracting bacterial resistance mechanisms. In addition, emerging developments in the antibacterial pipeline—covering new, withdrawn, discontinued, and clinically advancing compounds (2000–2025)—are highlighted to reflect the current state of innovation in antibiotic discovery. By integrating chemical, pharmacological, and developmental insights, this review aims to provide a clear and updated perspective on how medicinal chemistry continues to shape the design and evolution of antibacterial therapeutics in the face of rising resistance.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 5","pages":"1279-1329"},"PeriodicalIF":13.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863406","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}

{"title":"Advancing Therapies for Mycobacterial Diseases: From Small Molecules to Host-Directed Strategies.","authors":"Tânia Silva, Alessandra Aiello, Tonino Alonzi, M Alice Carvalho, Vladimir Finger, Delia Goletti, Sven Hoffner, Yousra Kherabi, Jan Korabecny, Julia Kulczyńska, Agnieszka Kyzioł, Alicia Lacoma, Filomena Martins, Zorica Nanovic, Sepideh Hosseiniporgham, Martina Hrast Rambaher, Leonardo Antonio Sechi, Daria Smalchuk, Grażyna Stochel, Lydia Tabernero, Nancy L Tateosian, Violeta Valcheva, Anamarija Zega, Mafalda Sarraguça","doi":"10.1002/med.70096","DOIUrl":"https://doi.org/10.1002/med.70096","url":null,"abstract":"<p><p>The global burden of multidrug-resistant tuberculosis (MDR-TB) and the rising incidence of nontuberculous mycobacterial (NTM) infections highlight the urgent need for innovative therapeutic strategies. Current treatments are prolonged, toxic, and increasingly compromised by resistance and limited diagnostic capacity. This review focuses on emerging therapeutic strategies against Mycobacterium tuberculosis (Mtb) and highlights evidence relevant to NTM whenever available. Specifically, it explores direct anti-mycobacterial small molecules, including the optimization of drug classes, such as hydrazide-hydrazones, isoniazid derivatives, nitrofurans, multicomponent forms, and metal complexes, as well as emerging chemical entities in early-stage development. These compounds target essential bacterial enzymes such as decaprenylphosphoryl-β-d-ribose oxidase (DprE1), enoyl acyl carrier protein reductase (InhA), and deoxyribonucleic acid (DNA) gyrase inhibitors, offering promising avenues for overcoming resistance. The review also examines natural products and phytochemicals, including siderophore inhibitors, plant-derived compounds, and essential oils. Non-classical strategies such as antimicrobial peptides (AMPs) and phage therapy are also discussed. Finally, we discuss the expanding field of host-directed therapies (HDTs), which aim to modulate the host immune response to enhance mycobacterial clearance and reduce tissue damage. Ultimately, advancing mycobacterial treatment will require integrated, mechanism-based regimens that combine new compounds with HDTs and improved delivery systems. Although therapeutic innovation for NTM has lagged, adapting promising TB-focused compounds and implementing NTM-specific screening and validation frameworks are essential. Collaborative efforts across academia, industry, and the public health sector will be key to translating these advances into shorter, safer, and more effective therapies that address the complexity of mycobacterial disease and the rise of antimicrobial resistance.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672841","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}