Medicinal Research Reviews最新文献

{"title":"Aldo-Keto Reductase Family 1 Member B10 as a Therapeutic Frontier: Advances in Inhibitor Design and Multimodal Approaches","authors":"Jikuan Shao,&nbsp;Xiaolong Wang,&nbsp;Can Guo,&nbsp;Shuaishuai Xing,&nbsp;Haopeng Sun","doi":"10.1002/med.70050","DOIUrl":"10.1002/med.70050","url":null,"abstract":"<div>\u0000 \u0000 <p>Aldo-keto reductase 1B10 (AKR1B10), a key member of the aldehyde-ketone reductase superfamily, plays crucial roles in tumorigenesis, chemotherapy resistance, and metabolic regulation. However, the clinical translation of its inhibitors has been persistently hindered by off-target toxicities arising from highly homologous enzymes and severe competition from intracellular substrates. This review critically summarizes the paradigm shift in AKR1B10-targeted drug discovery. From a structural pharmacology perspective, we systematically elucidate how inhibitor design has evolved from classical anion-binding pocket (ABP) anchoring to pocket-specific designs that exploit the topological differences of subpockets (LAS/SP) to overcome subtype selectivity barriers. Furthermore, to bypass the inherent limitations of reversible competitive inhibition, we prospectively explore next-generation therapeutic modalities, including targeted protein degradation (PROTACs), covalent modifiers, and small molecule–drug conjugates (SMDCs), alongside multitarget combination regimens aimed at systematically dismantling tumor resistance networks. Ultimately, this review aims to provide breakthrough insights to overcome current clinical bottlenecks, providing a reference for the future development of novel, highly efficacious precision oncology therapeutics.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"1005-1025"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589070","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":"Biodegradable Natural Polymer-Based Drug Delivery Systems for Bone Tissue Engineering","authors":"Hyejin Jo,&nbsp;Shinwon Kang,&nbsp;Jae Eun Yang,&nbsp;Inseon Kim,&nbsp;Seunghun S. Lee","doi":"10.1002/med.70039","DOIUrl":"10.1002/med.70039","url":null,"abstract":"<p>The increasing incidence of bone diseases and injuries, especially among aging populations, has underscored the shortcomings of traditional treatments such as bone grafts and metal implants, which often face complications including immune rejection, mechanical failure, and delayed healing. In response, drug delivery systems incorporated into biomaterial scaffolds have emerged as a promising strategy to enhance therapeutic efficacy and promote bone regeneration. This review provides a comprehensive overview of biodegradable natural polymer-based scaffolds, focusing on their structural characteristics and drug delivery capabilities in bone tissue engineering. Four principal scaffold architectures—sponges, nanofibers, hydrogels, and microspheres—are examined with respect to their regenerative functionality, associated limitations, and recent engineering advancements. In particular, we discuss the use of four representative natural polymers—collagen, cellulose, chitosan, and hyaluronic acid—and their physicochemical properties that contribute to osteogenesis. Furthermore, recent strategies for enhancing scaffold performance can be broadly divided into two categories. First, nanostructured approaches that reinforce the intrinsic functionality of natural polymers, such as MXene-polymer nanocomposites, halloysite nanotube-loaded hydrogels, and nanocrystalline cellulose systems, have improved drug delivery efficiency and mechanical resilience. Second, advances in three-dimensional (3D) scaffold fabrication—including electrospinning, freeze-drying, 3D printing, bioplotting, photolithography, and microfluidics—have enabled precise control over scaffold architecture, porosity, and biomolecule positioning. Together, these strategies represent critical developments for designing next-generation bone tissue engineering platforms.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"966-988"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508175","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":"Comparative Pharmacology of Caspase-1 Inhibitors: Ac-YVAD-CMK, Z-YVAD-FMK, and Ac-YVAD-CHO in Multisystem Diseases","authors":"Yujia Zheng,&nbsp;Baolei Dou,&nbsp;Yifan Ren,&nbsp;Xiangyi Zhang,&nbsp;Ruifeng Zhang,&nbsp;Guangming Zhang,&nbsp;Lin Yang,&nbsp;Miao Zeng,&nbsp;Jiali Gan,&nbsp;Xijuan Jiang,&nbsp;Pengjuan Xu","doi":"10.1002/med.70045","DOIUrl":"10.1002/med.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>Cysteine-aspartic protease-1 (Caspase-1), the terminal effector of canonical inflammasome signaling, represents a validated yet pharmacologically underexploited target at the convergence of inflammatory pathology and pyroptotic cell death. Although three peptide-based inhibitors—Ac-YVAD-CMK, Z-YVAD-FMK, and Ac-YVAD-CHO—have long served as prototypical experimental standards, their structural determinants, structure-activity relationships, and developmental liabilities have not been systematically reassessed from a medicinal chemistry perspective. Integrating evidence from 144 studies (2015–2025), this review rigorously interrogates these archetypal scaffolds as both pharmacological probes and foundational templates for inhibitor design. We delineate how C-terminal warhead chemistry (chloromethyl ketone, fluoromethyl ketone, and aldehyde) dictates covalency, reversibility, and kinetic selectivity, while N-terminal capping strategies modulate membrane permeability, metabolic stability, and systemic exposure. By correlating chemical architecture with caspase selectivity, off-target engagement, and context-dependent efficacy across inflammatory, infectious, autoimmune, and oncologic models, we define structure-kinetics-pharmacology relationships that govern selectivity, durability, and in vivo predictability. Persistent barriers—including inadequate pharmacokinetic characterization, metabolic fragility, broad caspase cross-reactivity, and limited scaffold diversification—are identified as principal impediments to the clinical translation of all three prototypical inhibitors. By repositioning these legacy peptide inhibitors as foundational chemical templates for translational optimization, this synthesis establishes design principles centered on kinetic selectivity, rational warhead refinement, and context-guided optimization, and outlines strategic pathways for the development of selective, clinically viable Caspase-1-targeted therapeutics.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"1071-1110"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621161","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":"CRISPR-Cas9 Genome-Wide Screening in Paediatric Cancer: Functional Genomics for Target Discovery and the Improvement of Existing Therapies","authors":"Steven He,&nbsp;Patrick Connerty,&nbsp;Antoine de Weck","doi":"10.1002/med.70046","DOIUrl":"10.1002/med.70046","url":null,"abstract":"<p>CRISPR-Cas9 genome-wide screening has been instrumental towards identifying novel targets for drug discovery in cancer research. However, much of this research has centred specifically on adult cancers, with paediatric cancers being underserviced by current research and screening. With contemporary evidence increasingly highlighting the differences in biology between adult and children's cancers, more research has gradually occurred investigating dependencies and mechanisms of resistance in paediatric cancers through the use of CRISPR-Cas9 genome-wide screens. This review collates and summarises the experimental genome-wide screens that have been performed specifically in paediatric cancer models, and highlights the versatility of this technology and the knowledge gained through this research.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"989-1004"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147579939","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":"Mucin O-Glycosylation and Mucolytic Therapies in Pseudomyxoma Peritonei: Literature Review","authors":"Qi-Di Zhao,&nbsp;David L. Morris,&nbsp;Zheng-Long Sun,&nbsp;Yan Li","doi":"10.1002/med.70051","DOIUrl":"10.1002/med.70051","url":null,"abstract":"<div>\u0000 \u0000 <p>Effective mucolytic therapy can greatly improve the efficacy of cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, alleviate symptoms and improve prognosis for pseudomyxoma peritonei (PMP) patients. The main components of PMP mucus are highly O-glycosylated proteins called mucins. Represented by mucin2 (MUC2), mucins are the source of mucus viscoelasticity. This review investigated detailed processes of mucin O-glycosylation and mucolytic therapies in PMP. We introduced molecular pathological mechanism of PMP, types of mucus and mucins in PMP, molecular structure and biological functions of mucins. We focus on the synthesis process and physiological functions of MUC2 O-glycosylation. Furthermore, we summarize the potential therapeutic approaches to inhibiting mucin secretion and mucolysis. Detailed process of mucin O-glycosylation in endoplasmic reticulum and Golgi apparatus was discussed. We discussed promising approaches to targeting the substrates and enzymes in O-glycosylation, including uridine diphosphate and GalNAc analogs/derivatives, ppGalNAc-T/GALNT inhibitors, disulfide bond reducing agents or PDI inhibitors, O-glycosidases, and glucoproteinases. We provide a reference for the development of PMP mucolytic therapy, and some potential therapeutic targets aiming at mucin O-glycosylation.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"1152-1172"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632004","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":"Urologic Bacteriome: The Hero or the Villain in Prostate Cancer Onset, Progression, and Treatment?","authors":"Lara R. S. Fonseca,&nbsp;Mariana Feijó,&nbsp;Cátia V. Vaz,&nbsp;Bruno J. Pereira,&nbsp;Sandra Laurentino,&nbsp;Ana Palmeira-de-Oliveira,&nbsp;Sílvia Socorro","doi":"10.1002/med.70042","DOIUrl":"10.1002/med.70042","url":null,"abstract":"<p>Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide and the fifth leading cause of cancer-related mortality, presenting urgent unmet clinical needs in diagnosis and treatment. The recognition of the microbiome as a key factor in human health has prompted numerous studies, revealing an exciting new approach to cancer diagnosis and therapy. The bacteriome is the component of the microbiome that is most metabolically active and influenceable by internal and external factors, which is pivotal in the development of cancer. Initial studies exploring the link between the microbiome and PCa focused primarily on the gut bacteriome, which has been implicated in the onset and progression of the disease, as well as in resistance to therapy. Further research has demonstrated that the urologic bacteriome also plays a crucial role in the development of PCa, serving as an important factor for diagnosis and treatment. This review synthesizes current knowledge concerning the significance of the urologic bacteriome in PCa onset, progression, diagnosis/prognosis, and therapy. It also explores the impact of the bacterial metabolome in PCa, emphasizing the importance of this undervalued dimension of the bacteriome. Overall, the review provides a comprehensive analysis of how bacteria and their bioactive metabolites contribute to PCa, highlighting their clinical and therapeutic relevance. It also identifies the existing knowledge gaps, paving the way for the development of new approaches that could enhance PCa diagnosis and treatment.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"1111-1151"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626488","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":"Unlocking Multiscale Allosteric Mechanisms: Advanced Computational Strategies for Drug Discovery","authors":"Ruidi Zhu,&nbsp;Chengwei Wu,&nbsp;Mingyu Li,&nbsp;Xinyi Liu,&nbsp;Jian Zhang","doi":"10.1002/med.70036","DOIUrl":"10.1002/med.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiscale allosteric mechanisms refer to regulatory processes in proteins that involve coordinated conformational changes and signal transmission occurring across multiple spatial and temporal scales. Exploiting these mechanisms provides promising opportunities in drug discovery due to potential advantages such as increased selectivity and fewer side effects compared to traditional orthosteric targeting. Nevertheless, systematically identifying allosteric sites and accurately deciphering their regulatory pathways remain challenging because these sites are often cryptic and regulated through intricate dynamic networks. Recent advances in computational methods, including multiscale molecular dynamics simulations, enhanced sampling techniques, topological network models, and machine learning-based analyses, have significantly improved our understanding of these multiscale allosteric phenomena. Here, we comprehensively summarize state-of-the-art computational strategies applied to the study of multiscale allosteric mechanisms and highlight their direct implications for drug discovery. Through representative examples, we demonstrate how computational approaches facilitate the identification of hidden allosteric sites, unravel complex regulatory pathways, and address issues related to drug resistance driven by mutations. Finally, we discuss the necessity of integrating these computational insights with experimental validation, underscoring a synergistic approach to accelerate the rational design and optimization of novel allosteric therapeutics.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"836-852"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176769","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":"Immunosuppressive Tumor Microenvironment and Therapeutic Landscape of Diffuse Intrinsic Pontine Glioma","authors":"Shuyi Zhou,&nbsp;Sandro Matosevic","doi":"10.1002/med.70037","DOIUrl":"10.1002/med.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive and fatal pediatric brainstem tumor, characterized by rapid progression and extremely poor prognosis. Its infiltrative growth within the pons, combined with the critical function and inaccessibility of the brainstem, makes surgical resection different and significantly limits therapeutic options. Moreover, the molecular and cellular heterogeneity of DIPG complicates therapeutic development, and despite decades of research, the current standard of care remains limited to palliative radiotherapy. In recent years, tumor immunology in DIPG has gained attention, as its immunosuppressive microenvironment, resulting in an immunologically ‘cold’ tumor, presents both a challenge and an opportunity for advancing immunotherapeutic strategies. In this review, we focus on outlining what is known about the developmental biology, pathological hallmarks, and immunosuppressive tumor microenvironment of DIPG, including immune infiltration and function of both immunosuppressive cells and effector NK and T cells. We also summarize recent advances in the therapeutic landscape of DIPG, including targeted therapies (epigenetic modulators, receptor tyrosine kinase inhibitors, cell cycle and DNA damage response inhibitors, metabolic immune modulators), immunotherapies (adoptive cell therapy, immune checkpoint inhibitors, vaccine therapy and oncolytic virotherapy), and novel delivery approaches currently under preclinical and clinical investigation. Emerging trends highlight the potential of combination therapies to enhance treatment efficacy. A deeper understanding of DIPG biology and tumor microenvironment is critical for advancing more effective therapies for this aggressive disease among these vulnerable populations.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 4","pages":"896-920"},"PeriodicalIF":11.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388860","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":"Respiratory Syncytial Virus (RSV): A Comprehensive Overview From Basic Biology to Clinical Prevention and Control","authors":"Jie Shi,&nbsp;Xiya Huang,&nbsp;Chunjun Ye,&nbsp;Yishan Lu,&nbsp;Yanyan Liu,&nbsp;Yuquan Wei,&nbsp;Xiawei Wei","doi":"10.1002/med.70025","DOIUrl":"10.1002/med.70025","url":null,"abstract":"<p>Respiratory syncytial virus (RSV) is a common virus that causes respiratory infections, posing a serious threat, particularly to infants, the elderly, and individuals with compromised immune systems. As the leading cause of lower respiratory tract infections (LRTIs) in infants, RSV is responsible for millions of cases worldwide each year. Its incidence rises significantly during the winter influenza season. Despite decades of research, no effective vaccine exists, and antiviral treatment options remain limited, presenting a major challenge to global public health. With the advancement of emerging technologies, researchers have made significant progress in understanding the pathological and biological characteristics of RSV, the mechanisms of immune response, and its long-term health impacts. This review aims to provide a comprehensive overview of the basic biological characteristics, epidemiology, clinical manifestations, and diagnostic and therapeutic strategies of RSV and to explore preventive measures and future research directions, offering the latest scientific evidence for RSV prevention and control.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 3","pages":"672-712"},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556076","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":"Front Cover Image, Volume 46, Issue 3","authors":"Jiayi Deng,&nbsp;Yasi Deng,&nbsp;Yuxin Chen,&nbsp;Fan Bai,&nbsp;Bowen Zhang,&nbsp;Wuyang Jiang,&nbsp;Wei Wang,&nbsp;Huanghe Yu","doi":"10.1002/med.70044","DOIUrl":"https://doi.org/10.1002/med.70044","url":null,"abstract":"<p>The cover image is based on <i>The IL-23/IL-17/NF-κB Signaling Pathway in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Agents</i> by Jiayi Deng et al., https://doi.org/10.1002/med.70024.\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 3","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147686850","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}