Medicinal Research Reviews最新文献

{"title":"Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.","authors":"Luisa Racca, Gianluca Baldanzi, Alberto Massarotti","doi":"10.1002/med.70010","DOIUrl":"https://doi.org/10.1002/med.70010","url":null,"abstract":"<p><p>Catalyzing the conversion of diacylglycerol (DAG) in phosphatidic acid (PA), diacylglycerol kinases (DGKs) play a pivotal role in all the physiological processes modulated by these two bioactive lipids, such as lipid metabolism and immune regulation. Consequently, abnormalities due to a dysregulation of DGK's activity are involved in several pathological contexts, from cancer to autoimmune diseases. Interestingly, ten DGK isoforms with specific structure and expression pattern are present in humans, suggesting nonredundant roles. Despite their potential as therapeutic targets, the possibility of selective DGK pharmacological modulation remains limited to two isoforms. However, the research for DGK isoform-specific modulators is growing, as well as the interest in the structure and functioning of all DGK family members. This review aims to present all the information on DGK modulators, from the literature to patents' databases, starting from what we know about DGK's structure, the key physiological and pathological processes where they are involved and, above all, to understand which are nowadays the possibilities for DGK activation/inhibition. Our aim is to inspire future investigations which could accelerate the discovery of new DGK-targeting compounds.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937325","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":"Digital Therapeutics for Alzheimer's and Parkinson's Diseases: Current Trends and Future Perspectives.","authors":"Yoo Joo Jeong, Hyun-Ju Lee, Jun-Su Kim, Seung-Jae Kim, Unhui Jo, Jin Yeop Park, Su Jin Jun, Won Seok Lee, Mingoo Song, Donggii Kim, Gyoujin Cho, Jeong-Heon Song, Hyang-Sook Hoe","doi":"10.1002/med.70005","DOIUrl":"https://doi.org/10.1002/med.70005","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and Parkinson's disease (PD), which are characterized by the accumulation of misfolded protein aggregates and cognitive/motor dysfunction, are the most prevalent neurodegenerative diseases (NDDs). Despite strategic investigations aimed at augmenting the pharmaceutical pipeline, available drugs for AD and PD merely slow disease progression without curing or treating the underlying pathology. Recent technological advances have given rise to digital therapeutics (DTx): software systems that aim to prevent, cure, and manage specific diseases, including NDDs. For AD and PD, the majority of DTx focus on enhancing cognitive/executive function and motor-related functions, respectively. In this review, we describe the status of therapeutic development for AD and PD, as well as the characteristics and status of DTx targeting these NDDs. In addition, we address the limitations and challenges of DTx and their implications for the treatment of AD and PD. Ultimately, this review provides insights into the potential of DTx as a therapeutic modality and future directions for the development of DTx targeting AD and PD.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758816","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":"Structural Properties, Pathophysiological Relevance and Synthetic Modulators of TRPC Channels.","authors":"Xue Qiao, Chunlin Ren, Wumei Wang, Xiaofen Wang, Guo-Bo Li, Cheng Chen, Bengui Ye, Xiaodong Zeng, Yuling Xiao, Xuechuan Hong","doi":"10.1002/med.70007","DOIUrl":"https://doi.org/10.1002/med.70007","url":null,"abstract":"<p><p>Transient receptor potential canonical (TRPC) channels, a subfamily of calcium-permeable cation channels, regulate diverse physiological processes and are implicated in disorders including neurological conditions, cardiovascular diseases, and chronic kidney disease. Recent advances in cryo-electron microscopy (cryo-EM) have elucidated TRPC structures, while subtype-selective modulators have clarified their pathophysiological roles and therapeutic potential. This review integrates the structural and functional attributes of TRPC channels, emphasizing their contributions to health and disease. We highlight synthetic strategies and structure-activity relationships driving the development of selective pharmacological tools, several of which show preclinical promise. By uniting TRPC biology with medicinal chemistry, this study provides strategic guidance for advancing clinically viable TRPC-targeted therapeutics.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740756","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":"Advances in Nanotechnology-Enabled Optical Biosensors for Dengue Virus Detection: A Systematic Review.","authors":"Marta Quero-Delgado, Helena Codina, Rafael Gómez, Francisco José Terán, M A Muñoz-Fernández, José Luis Jiménez, Salvador Resino, Daniel Sepúlveda-Crespo, Isidoro Martínez","doi":"10.1002/med.70006","DOIUrl":"https://doi.org/10.1002/med.70006","url":null,"abstract":"<p><p>The dramatic surge in dengue cases in early 2024, endangering half the global population, urgently necessitates faster diagnostic methods. Nanotechnology-enabled optical biosensors offer a promising avenue, leveraging nanomaterial properties for highly sensitive detection of dengue virus (DENV), potentially surpassing conventional techniques in terms of simplicity, speed, and cost-effectiveness. This systematic review analyzes recent advancements in these biosensors for DENV diagnosis. Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases (2010-June 1, 2025; OSF: https://osf.io/3gmey/). The methodological quality of the 98 included studies was assessed using a modified CASP checklist. Diverse nanotechnology-based optical biosensors were identified. SPR (36.7%) was the most common transducer, followed by fluorescence (24.5%), colorimetry (15.3%), and SERS (8.2%). Gold-based nanomaterials (35.7%) were most frequently employed, with silver nanomaterials (15.3%), quantum dots (15.3%), and graphene-based materials (15.3%) also showing promise. DENV NS1 protein was the primary target analyte (21.4%). Importantly, almost half of the studies (44.9%) used clinically relevant human samples. While many optical biosensors show promise, challenges hinder their demonstration of the true potential for point-of-care use in their current format; however, they offer high specificity and faster results, laying a strong foundation for cost-effective clinical diagnostics. Nanotechnology-driven optical biosensors offer a transformative approach for DENV detection. Advances in computational design and green synthesis of novel nanomaterials are key to addressing stability and field-deployment challenges. These innovations are crucial for developing robust, sensitive, and user-friendly tools to manage dengue and improve patient outcomes globally.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740755","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":"Recent Progress in the Discovery of Anti-Mpox Agents.","authors":"Le Wang, Tao Zhang, Na Wang, Xinyong Liu, Dongwei Kang","doi":"10.1002/med.70004","DOIUrl":"https://doi.org/10.1002/med.70004","url":null,"abstract":"<p><p>The monkeypox (mpox) outbreak has once again become a Public Health Emergency of International Concern, increasing the focus of research on the development of anti-monkeypox drugs. Monkeypox virus (MPXV) is a member of the Orthopxviridae genus, which also contains the variola virus, cowpox virus, and vaccinia virus. As no specific drugs for mpox are available, tecovirimat and brincidofovir for the treatment of smallpox infection are recommended to treat Mpox infection. The purpose of this review is to provide reference for further development of Mpox virus antiviral drugs by summarizing the resolving Mpox virus target protein structures and its mechanism of action, drugs with potential anti-Mpox virus activity, in vitro and in vivo inhibitory activity detection methods of anti-Mpox virus drugs, and the prevention of drug resistance. We hope to facilitate the discovery of antiviral drugs for MPXV by providing insights into the further development of appropriate anti-Mpox drugs based on currently available viral protein targets.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726273","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":"The Discovery of Cryptic Pockets Increases the Druggability of \"Undruggable\" Proteins.","authors":"Minyue Mou, Weicheng Yang, Guangyi Huang, Xiaoyan Yang, Xiao Zhang, Wasala Mudiyanselage Wishwajith Wickramabahu Kandegama, Charles R Ashby, Gefei Hao, Yangyang Gao","doi":"10.1002/med.70001","DOIUrl":"https://doi.org/10.1002/med.70001","url":null,"abstract":"<p><p>The absence of suitable biological targets is one of the most formidable obstacles to drug development. The investigation of \"undruggable\" proteins has the potential to significantly increase the druggable proteome. Cryptic pockets represent specific potential pockets that provide a rare opportunity to target \"undruggable\" proteins. The identification of cryptic pockets, in combination with drug design studies, has made significant progress, especially due to the emergence of artificial intelligence (AI) technology. However, there has been no comprehensive review of the methods and successful identification of cryptic pockets and associated inhibitors for \"undruggable\" targets. Here, we systematically summarize and analyze the latest strategies for identifying cryptic pockets and designing related inhibitors. First, we analyze both computational methods and experimental approaches for the discovery of cryptic pockets or regions. We will also discuss studies that have successfully identified specific cryptic pockets and developed compounds that inhibit the \"undruggable\" targets, using these as successful case studies. The limitations, drawbacks, and underlying trends in cryptic pocket identification and inhibitor design will also be discussed. We anticipate that this article will guide biologists and chemists in efficiently and accurately identifying cryptic pockets present in \"undruggable\" targets to facilitate relevant drug discovery.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641341","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":"A Focus on Natural Autophagy Modulators as Potential Host-Directed Weapons Against Emerging and Re-Emerging Viruses.","authors":"Ilaria Cursaro, Sara Rossi, Stefania Butini, Sandra Gemma, Gabriele Carullo, Giuseppe Campiani","doi":"10.1002/med.70003","DOIUrl":"https://doi.org/10.1002/med.70003","url":null,"abstract":"<p><p>Autophagy is a highly conserved intracellular process involved in maintaining homeostasis and in the degradation of damaged organelles and external pathogens. Nature provides complex and varied reservoirs of scaffolds and chemical entities that may have a pivotal role in the search for new therapeutic leads. Among them, phytocompounds have been amply exploited in the search for new autophagy modulators to tackle diseases like cancer and degenerative disorders, while their use as potential antiviral agents has been explored to a limited extent. The modulation of autophagy in viral infections may play a dual and contraposing role. Depending on the replication mechanism of the virus, it may serve as an adjuvant in the innate immune response of the host, or it may be hijacked by viruses, favoring their replication. This review is intended to present an overview of antiviral natural compounds and extracts capable of modulating autophagy, and it seeks to provide a solid foundation for researchers to further investigate the mechanisms of autophagy modulation during viral infections and to identify diverse molecular entities for antiviral drug discovery.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641340","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":"Comprehensive Insights Into Sulfanilamido-Based Medicinal Design and Research.","authors":"Yi-Xin Wang, Juan Wang, Lin-Li Mou, Hui-Zhen Zhang, Guang-Ying Chen, Cheng-He Zhou","doi":"10.1002/med.22115","DOIUrl":"https://doi.org/10.1002/med.22115","url":null,"abstract":"<p><p>The sulfanilamido skeleton is the core part of many clinical drugs with the para-aminobenzenesulfamido scaffold. Especially as the first type of synthetic antibacterial drugs, sulfanilamides have played important roles in preventing and treating infectious diseases for more than 90 years. Increasing efforts have been contributing toward the sulfanilamido skeleton with the incorporation of various unique substituents through medicinal design, which accessed great achievements that have not only broken the classical structure-activity relationship of antibacterial sulfanilamides, but also extended the other medicinal applications of sulfanilamides except for antibacterial drugs. Recently, the sulfanilamido-based medicinal design and research are becoming increasingly active, which have aroused widespread concern in the medicinal community. Thus, based on our work on sulfanilamido skeleton, this review article encompasses a robust collection of 746 references from 2008 to the present and, for the first time, provides comprehensive insights into sulfanilamido-based medicinal design and research across a wide range of medicinal potential. It is involved in antibacterial, antifungal, antitubercular, antiviral, anticancer, anti-inflammatory, antiglaucoma, antiparasitic, psychotherapeutic, antidiabetic, and other medicinal aspects. It also covers a large amount of sulfanilamido-based rich information on medicinal chemistry, including some important clinical sulfanilamido-based drugs, sulfanilamido-based medicinal molecular design strategies, structure-activity relationships, some important action targets, some important action mechanisms, as well as a multitargeting medicinal design strategy and medicinal chemicobiology. The foreseeable future research directions and trends toward medicinal design and development of sulfanilamido skeleton are prospected. This work might provide beneficial help for sulfanilamido-based rational design and development to afford sulfanilamido-based drugs with broad spectrum, high biological activity, and low toxicity to treat various diseases worldwide.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599009","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":"How Artificial Intelligence Assists in Overcoming Drug Resistance?","authors":"Ferdinand Ndikuryayo, Xue-Yan Gong, Ge-Fei Hao, Wen-Chao Yang","doi":"10.1002/med.70002","DOIUrl":"https://doi.org/10.1002/med.70002","url":null,"abstract":"<p><p>The increasing prevalence of drug resistance (DR) and pesticide resistance poses a significant threat to public health, necessitating the development of innovative strategies to discover more effective drugs and pesticides. In this context, artificial intelligence (AI) has emerged as a promising solution. This review examines the roles of AI in tackling DR. An analysis of current literature reveals that AI can enhance the drug discovery process, facilitating the faster creation of effective and safer medications. Furthermore, AI is crucial in predicting and elucidating the mechanisms of DR and pesticide resistance. By offering decision support to healthcare providers, AI-driven precision medicine paves the way for personalized treatment options. Moreover, AI aids in identifying synergistic drug combinations essential for combating DR. Lessons from the recent use of AI in addressing DR demonstrate the potential of this versatile tool to offer solutions required for controlling infections and cancers in the era of DR. However, despite the advancements achieved, challenges such as data accessibility and ethical issues remain. This highlights the need for interdisciplinary collaboration and ethical consideration. Finally, we provide an outlook on future actions required to successfully implement AI-powered technologies in drug and pesticide discovery.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558631","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":"Front Cover Image, Volume 45, Issue 4","authors":"Nicola Bauer,&nbsp;Qiyue Mao,&nbsp;Aditi Vashistha,&nbsp;Anupamaa Seshadri,&nbsp;Yi-Chieh Nancy Du,&nbsp;Leo Otterbein,&nbsp;Chalet Tan,&nbsp;Mark P. de Caestecker,&nbsp;Binghe Wang","doi":"10.1002/med.22124","DOIUrl":"https://doi.org/10.1002/med.22124","url":null,"abstract":"<p>The cover image is based on the article <i>Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide</i> by Nicola Bauer et al., https://doi.org/10.1002/med.22116.\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":"45 4","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197215","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}