Medicinal Research Reviews最新文献

{"title":"The Hsp90β Isoform: An Attractive Target for Drug Development.","authors":"Subhabrata Chaudhury, Terin D'Amico, Brian S J Blagg","doi":"10.1002/med.22114","DOIUrl":"https://doi.org/10.1002/med.22114","url":null,"abstract":"<p><p>The beta isoform of 90 kDa heat shock protein (Hsp90β) plays a critical role in maintaining cellular proteostasis by assisting in the folding and refolding of proteins, which is essential for both normal cellular function and stress response. It is constitutively expressed in mammalian cells, differentiating it from the inducible Hsp90α isoform. Hsp90β's involvement in diverse cellular processes, such as signal transduction, cell cycle control, and apoptosis, underscores its significant role in various diseases, including cancer and neurodegenerative disorders. The isoform-specific functions of Hsp90β and its interaction with unique client proteins make it a promising target for therapeutic intervention, particularly in the development of selective inhibitors that avoid the adverse effects observed with pan-Hsp90 inhibitors. This review delves into the structural and functional intricacies of Hsp90β, its role in disease, and the potential for selective drug development.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957956","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 Quinoline Photoremovable Group (PPG) Platform-A Medicinal Chemist's Approach for Photocage Development and Applications.","authors":"Bence Kontra, Zoltán Mucsi, Janez Ilaš, Petra Dunkel","doi":"10.1002/med.22111","DOIUrl":"https://doi.org/10.1002/med.22111","url":null,"abstract":"<p><p>Photoremovable protecting groups (PPGs) offer a straightforward solution for the temporary inactivation of biologically active substrates and their subsequent controlled release by light irradiation. Their relatively easy design and mode of application have made them useful tools for studying dynamic biological processes in vitro and in vivo. Recently, there has been a growing body of data investigating their potential application in the development of drug delivery systems. Of the various PPG scaffolds in use, quinoline photocages have a history of about 20 years. The structure-property relationships of quinoline PPGs, as well as alternative multibranch designs based on quinoline monomers have been thoroughly studied both experimentally and theoretically. Therefore, quinoline PPGs serve as a representative study of PPG development, showing how the various applications of quinoline photocages followed the chemical optimization or how the applications drove the chemical design. Since the raison d'être of PPGs lies in their application for light-activated release of various substrates or performing light-activated structural changes in materials, it is crucial to understand how PPGs are selected and utilized by their end-users, who are often not chemists themselves. Therefore, we discuss whether the conclusions drawn from the selected quinoline PPG family could lead to more general insights for the field as whole. As PPG-related applications still rely heavily on a limited number of chemical scaffolds, it is worth considering, what could be the reasons for the slow uptake of novel chemical scaffolds.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959249","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":"Molecular Tools to Study and Control Dopaminergic Neurotransmission With Light.","authors":"Galyna Maleeva, Carlo Matera, Silvia Roda, Alessio Colleoni, Marco De Amici, Pau Gorostiza","doi":"10.1002/med.22112","DOIUrl":"https://doi.org/10.1002/med.22112","url":null,"abstract":"<p><p>Dopaminergic neurotransmission is involved in several important brain functions, such as motor control, learning, reward-motivated behavior, and emotions. Dysfunctions of dopaminergic system may lead to the development of various neurological and psychiatric disorders, like Parkinson's disease, schizophrenia, depression, and addictions. Despite years of sustained research, it is not fully established how dopaminergic neurotransmission governs these important functions through a relatively small number of neurons that release dopamine. Light-driven neurotechnologies, based on the use of small light-regulated molecules or overexpression of light-regulated proteins in neurons, have greatly contributed to the advancement of our understanding of dopaminergic circuits and our ability to control them selectively. Here, we overview the current state-of-the-art of light-driven control of dopaminergic neurotransmission. While we provide a concise guideline for the readers interested in pharmacological, pharmacogenetic, and optogenetic approaches to modulate dopaminergic neurotransmission, our primary focus is on the usage of photocaged and photo-switchable small dopaminergic molecules. We argue that photopharmacology, photoswitchable molecules of varied modalities, can be employed in a wide range of experimental paradigms, providing unprecedent insights into the principles of dopaminergic control, and represent the most promising light-based therapeutic approach for spatiotemporally precise correction of dopamine-related neural functions and pathologies.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959672","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":"Marine Natural Products in Inflammation-Related Diseases: Opportunities and Challenges.","authors":"Tao Zhang, Zijun Ouyang, Yueran Zhang, Haiyan Sun, Lingdong Kong, Qiang Xu, Jiao Qu, Yang Sun","doi":"10.1002/med.22109","DOIUrl":"https://doi.org/10.1002/med.22109","url":null,"abstract":"<p><p>In recent decades, the potentiality of marine natural products (MNPs) in the medical field has been increasingly recognized. Natural compounds derived from marine microorganisms, algae, and invertebrates have shown significant promise for treating inflammation-related diseases. In this review, we cover the three primary sources of MNPs and their diverse and unique chemical structures and bioactivities. This review aims to summarize the progress of MNPs in combating inflammation-related diseases. Moreover, we cover the functions and mechanisms of MNPs in diseases, highlighting their functions in regulating inflammatory signaling pathways, cellular stress responses, and gut microbiota, among others. Meanwhile, we focus on key technologies and scientific methods to address the current limitations and challenges in MNPs.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954566","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 Bright Future for Photopharmaceuticals Addressing Central Nervous System Disorders: State of the Art and Challenges Toward Clinical Translation.","authors":"Rudolf L Z Ganzoni, Sofie S Bournons, Erick M Carreira, Dimitri De Bundel, Ilse Smolders","doi":"10.1002/med.22105","DOIUrl":"https://doi.org/10.1002/med.22105","url":null,"abstract":"<p><p>Photopharmacology is an innovative approach that uses light to activate drugs. This method offers the potential for highly localized and precise drug activation, making it particularly promising for the treatment of neurological disorders. Despite the enticing prospects of photopharmacology, its application to treat human central nervous system (CNS) diseases remains to be demonstrated. In this review, we provide an overview of prominent strategies for the design and activation of photopharmaceutical agents in the field of neuroscience. Photocaged and photoswitchable drugs and bioactive molecules are discussed, and an instructive list of examples is provided to highlight compound design strategies. Special emphasis is placed on photoactivatable compounds for the modulation of glutamatergic, GABAergic, dopaminergic, and serotonergic neurotransmission for the treatment of neurological conditions, as well as various photoresponsive molecules with potential for improved pain management. Compounds holding promise for clinical translation are discussed in-depth and their potential for future applications is assessed. Neurophotopharmaceuticals have yet to achieve breakthrough in the clinic, as both light delivery and drug design have not reached full maturity. However, by describing the current state of the art and providing illustrative case studies, we offer a perspective on future opportunities in the field of neurophotopharmacology focused on addressing CNS disorders.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787421","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 Developments in the Optical Control of Adrenergic Signaling.","authors":"Shuang Shi, Yangzhi Cao, Maikel Wijtmans, Henry F Vischer, Rob Leurs","doi":"10.1002/med.22110","DOIUrl":"https://doi.org/10.1002/med.22110","url":null,"abstract":"<p><p>Adrenoceptors (ARs) play a vital role in various physiological processes and are key therapeutic targets. The advent of optical control techniques, including optogenetics and photopharmacology, offers the potential to modulate AR signaling with precise temporal and spatial resolution. In this review, we summarize the latest advancements in the optical control of AR signaling, encompassing optogenetics, photocaged compounds, and photoswitchable compounds. We also discuss the limitations of current tools and provide an outlook on the next generation of optogenetic and photopharmacological tools. These emerging optical technologies not only enhance our understanding of AR signaling but also pave the way for potential therapeutic developments.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778511","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":"Light-Activated Pharmacological Tools for Exploring the Cholinergic System","authors":"Alessio Colleoni,&nbsp;Giulia Galli,&nbsp;Clelia Dallanoce,&nbsp;Marco De Amici,&nbsp;Pau Gorostiza,&nbsp;Carlo Matera","doi":"10.1002/med.22108","DOIUrl":"10.1002/med.22108","url":null,"abstract":"<p>Cholinergic transmission plays a critical role in both the central and peripheral nervous systems, affecting processes such as learning, memory, and inflammation. Conventional cholinergic drugs generally suffer from poor selectivity and temporal precision, leading to undesired effects and limited therapeutic efficacy. Photopharmacology aims to overcome the limitations of traditional drugs using photocleavable or photoswitchable ligands and spatiotemporal patterns of illumination. Spanning from muscarinic and nicotinic modulators to cholinesterase inhibitors, this review explores the development and application of light-activated compounds as tools for unraveling the role of cholinergic signaling in both physiological and pathological contexts, while also paving the way for innovative phototherapeutic approaches.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"45 4","pages":"1251-1274"},"PeriodicalIF":10.9,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690748","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":"Danshensu Derivatives: A Series of Promising Drugs With Protective Effects Against Cardiocerebrovascular Diseases and Cancers","authors":"Yang Yang,&nbsp;Luyang Du,&nbsp;Huadong Zhao,&nbsp;Ye Zhao,&nbsp;Sha Liao,&nbsp;Zhe Zhang,&nbsp;Shaofei Zhang,&nbsp;Yajun Bai,&nbsp;Xiaohui Zheng","doi":"10.1002/med.22102","DOIUrl":"10.1002/med.22102","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Salvia miltiorrhiza</i> (Danshen in Chinese) is a traditional medicinal plant with an extensive range of cardiocerebrovascular protective effects widely used in China and other Asian countries. Danshensu (DSS) is the most important water-soluble component of Danshen and has significant antioxidant, anti-inflammatory, antiplatelet aggregation, antitumor, and other pharmacological activities. However, DSS has poor fat solubility and is unstable due to its <i>o</i>-phenol hydroxyl and α-hydroxy carboxylic acids. Therefore, it is necessary to develop new DSS derivatives through reasonable structural modifications to obtain new drugs with better activity, preferable stability, and higher bioavailability. Our team has previously investigated the effect of Danshen on chronic diseases. Through nearly two decades of research, we have made considerable research progress on the impact of DSS derivatives on cardiocerebrovascular diseases. Based on the published literature and our previous work, it was confirmed that DSS derivatives have a wide range of cardiocerebrovascular protective and other pharmacological effects. Here, this review summarized recent research progress on DSS derivatives in terms of design, synthesis, pharmacological effects, and molecular mechanisms to provide new insights for further research.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"45 4","pages":"1163-1183"},"PeriodicalIF":10.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603274","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":"Breaking Barriers; Phytoestrogens in the Fight Against Triple-Negative Breast Cancer: A Comprehensive Review","authors":"Md Sohel","doi":"10.1002/med.22107","DOIUrl":"10.1002/med.22107","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of standard drugs for some unusual cancers, including estrogen-nonresponsive breast cancer, is somewhat difficult within a very short time. So, considering the current situation, phytoestrogen may be a potential candidate for unraveling chemotherapeutics agents. The reason for this review article is to manifest overall information regarding the effects of phytoestrogen on triple-negative breast cancer (TNBC), along with its related cellular and molecular pathways in different TNBC models. Data was retrieved by systematic searches according to PRISMA guidelines, and commonly used tools and servers are BioRender, ChemDraw professional 16.0, Schrodinger, and ADMETlab 2.0. TNBC may be caused due to dysregulation of several signaling mechanisms such as Wnt/β-catenin, hedgehog, MAPK, notch, PI3K/AKT/mTOR, hippo, NF-κB, and JAK/STAT signaling cascades. Among all phytoestrogens (<i>n</i> = 150), 48 compounds are therapeutically effective on TNBC in some in vitro and preclinical models. Chemotherapeutics activities are regulated through varieties of mechanisms, including targeting signaling pathways such as phosphor-Akt, PI3K/AKT/mTOR, NF-κB, TNF-α; apoptosis such as FASL, Bcl2, Bax, Bak, Bad, apfa1, ASK1, Capase, and PARP; metastasis such as MMPs (1,2,3,9), Wnt/-β catenin, angiogenesis (E&amp;N Cadherin, Vimentin), cell proliferation (cyclins-A, B1, D1, E1, and CDKs 1, 6,7), inflammatory molecules (TNF-α, NF-κB, IL-1β, IL-8), regulating tumor suppressor genes (p21, p27, p51, p53) and some nonspecific pathways like DNA damage and repair (γH2AX, RAD51, and surviving), autophagy (mTOR, ULK1, and cathepsin B), epigenetic (HDAC1, DNMT1, telomerase production) and metabolism regulation (glucose regulation-GLUT1 and GLUT4), showing antioxidant and many other pathways. Some selective phytoestrogens exert synergistic activities with conventional cancer drugs as well radiotherapy like as conventional mechanism and reverse drug resistance through regulation of the EMT process, signaling pathways, drug sensitizing, miRNA regulation, and improving drug uptake. Nano-based phytoestrogen can target TNBC cells, stimulate drug accumulation, and improve drug efficacies, making phytoestrogens more effective agents in treating TNBC. Additionally, an in-silico pharmacokinetics study reveals that phytoestrogen possesses suitable pharmacokinetic characteristics with minor toxicity. So, phytoestrogen can be a potential candidate drug against TNBC until standard and fully effective pharma drugs are available at markets.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"45 4","pages":"1211-1250"},"PeriodicalIF":10.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603273","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":"Cutting-Edge Therapy and Immune Escape Mechanisms in EBV-Associated Tumors","authors":"Jie Wang,&nbsp;Rong Wang,&nbsp;Meifeng Wang,&nbsp;Junshang Ge,&nbsp;Yian Wang,&nbsp;Yanhan Li,&nbsp;Changan Chen,&nbsp;Jiale He,&nbsp;Boshu Zheng,&nbsp;Meifang Xu,&nbsp;Xianjie Jiang,&nbsp;Yuhang Liu,&nbsp;Mingfen Chen,&nbsp;Jun Long","doi":"10.1002/med.22104","DOIUrl":"10.1002/med.22104","url":null,"abstract":"<div>\u0000 \u0000 <p>Epstein–Barr virus (EBV), the first identified human tumor virus, significantly influences the immune microenvironment of associated cancers. EBV-induced expression of viral antigens by tumor cells triggers immune recognition and elicits a pro-inflammatory response. While mild inflammation may help eliminate malignant cells, intense inflammation can accelerate tumor progression. Moreover, EBV can establish lifelong latency in human hosts, characterized by low immunogenicity of its proteins and noncoding RNAs. This enables tumor cells to evade immune detection and impair immune cell function, disrupting immune homeostasis. Consequently, EBV-associated malignancies pose a considerable public health challenge globally, often complicating the prognosis of cancer patients under conventional treatment. With deeper research into the oncogenic expressions and mechanisms of EBV, novel targeted therapies against EBV are gaining prominence. This review discusses recent advancements in understanding how EBV helps tumor cells evade immune surveillance and induce immune dysfunction. It also examines the clinical potential of targeting EBV-associated tumors, providing fresh perspectives on the mechanisms and therapeutic strategies for these cancers.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"45 4","pages":"1184-1210"},"PeriodicalIF":10.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612710","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}