Medicinal Research Reviews最新文献_第3页

Advances in Antiviral Drug Development Targeting Viral Proteases 靶向病毒蛋白酶的抗病毒药物研究进展

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-07-06 DOI: 10.1002/med.70075

Yuanyuan Zhang, Jiaxin Chen, Jiaqi Li, Zhongxin Xu, Jing Wang, Luqing Shang

{"title":"Advances in Antiviral Drug Development Targeting Viral Proteases","authors":"Yuanyuan Zhang, Jiaxin Chen, Jiaqi Li, Zhongxin Xu, Jing Wang, Luqing Shang","doi":"10.1002/med.70075","DOIUrl":"10.1002/med.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Viral proteases are critical targets in antiviral drug development due to their essential role in the viral lifecycle and high conservation across viral strains. This review summarizes the recent progress of antiviral drugs based on protease structures, with a focus on the structural characteristics and inhibitor design strategies targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Enterovirus 71 (EV71), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Based on the three-dimensional structure of proteases, various types of protease inhibitors such as peptidomimetic, non-peptidic, and natural product-derived inhibitors are discussed. Given the critical challenge of drug resistance in antiviral therapies, we address the mechanisms of protease inhibitor resistance and explore advanced strategies, including allosteric inhibition, dual-target inhibition, and Proteolysis-Targeting Chimeras (PROTAC) to overcome drug resistance. This review also explores the cutting-edge applications of artificial intelligence (AI) for viral protease-based antiviral drug discovery, providing valuable insights for the rational design and development of antiviral drugs.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1871-1896"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395430","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}

引用次数: 0

A Possibility of Synthetic Lethality: Wee1 Kinase as a Promising Treating Target for Cancer 合成致死性的可能性：Wee1激酶有望成为治疗癌症的靶点。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-05-25 DOI: 10.1002/med.70057

Xin Xue, Xiao Chen, Yitian Jiang, Xinhai Wang, Zheng Xu, Chenqi Bei, Guanqiao Shi, Yifan Zhu, Yuqing Wei, Yao Chen, Nianguang Li

{"title":"A Possibility of Synthetic Lethality: Wee1 Kinase as a Promising Treating Target for Cancer","authors":"Xin Xue, Xiao Chen, Yitian Jiang, Xinhai Wang, Zheng Xu, Chenqi Bei, Guanqiao Shi, Yifan Zhu, Yuqing Wei, Yao Chen, Nianguang Li","doi":"10.1002/med.70057","DOIUrl":"10.1002/med.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>Wee kinases, including Wee1, Myt1 (PKMYT1) and Wee2, serve as critical regulators of the DNA damage response by inhibiting the G2/M transition and have attracted increasing attention as a targetable vulnerability in TP53-deficient cancers. Wee1 is the fastest progressing member in clinical research, and its inhibitors such as AZD-1775 and ZN-c3 are under clinical evaluation. Because toxicity and resistance persist with existing agents, research is moving toward newer strategies such as protein degradation technologies. Proceeding from sequence and structure, we, for the first time, use chemoinformatics to delineate the chemical space of the Wee1 binding pocket and classify reported inhibitors into three pocket engagement types, thereby constructing a high-resolution pocket map and an anchorable Markush for designing inhibitors with high selectivity and activity. We further summarize design principles for targeted degradation of Wee1 and outline combination strategies grounded in synthetic lethality, and we curate recent preclinical and ongoing clinical advances with discussion of biomarker-guided enrollment and dosing schedules. By linking structural mechanisms to pharmacology and clinical placement, this review provides an actionable framework for next-generation Wee1-directed drug design and translation in oncology.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1499-1542"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148012691","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}

引用次数: 0

Late INa as a Therapeutic Target: New Strategies, Computational Modelling, Drug Development, and Clinical Translation 晚期INa作为治疗靶点：新策略、计算模型、药物开发和临床翻译。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-07-17 DOI: 10.1002/med.70077

Arkapravo Chattopadhyay, Lynn C. Lunsonga, Peter E. Light, Khaled Barakat

{"title":"Late INa as a Therapeutic Target: New Strategies, Computational Modelling, Drug Development, and Clinical Translation","authors":"Arkapravo Chattopadhyay, Lynn C. Lunsonga, Peter E. Light, Khaled Barakat","doi":"10.1002/med.70077","DOIUrl":"10.1002/med.70077","url":null,"abstract":"<p>The Nav1.5 channel, a major isoform of voltage-gated sodium ion channel, is mainly found in ventricular cardiomyocytes, playing a key role in generating essential cardiac action potentials for normal heart rhythms. Mutations in Nav1.5 have been associated with severe heart conditions such as long QT syndrome, Brugada syndrome, cardiac conduction disorders, atrial fibrillation, and dilated cardiomyopathy. Recent research has linked Nav1.5 to cardiac fibrosis and proposed its role in non-cardiac illnesses, including specific neurological disorders and cancers, subjects that will be reviewed in this paper. On the other hand, sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially designed to manage diabetes by facilitating glucose excretion through urine, have demonstrated unexpected and encouraging cardioprotective benefits in clinical trials. This review compares the important SGLT2 inhibitors empagliflozin, dapagliflozin, and canagliflozin in terms of their interactions with Nav1.5 and their therapeutic effects on the heart. We also investigate new medications and compounds being developed to regulate Nav1.5 function, providing a preview of potential future treatments. Past attempts to develop late I<sub>Na</sub> inhibitors and difficulties in transitioning from the research phase to clinical trials have raised doubts about the optimal design of such trials. In addition, we cover the applications of molecular dynamics simulations in understanding the mechanism of action of these drugs within the Nav1.5 channel computationally. We hope that this review identifies new opportunities to generate more effective inhibitors using novel methods and advanced multiscale molecular modelling techniques.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1939-1957"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467969","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}

引用次数: 0

α-Synuclein Seeds Amplification Assays for Parkinson's Disease and Related Synucleinopathies 帕金森病及相关突触核蛋白病α-突触核蛋白种子扩增试验

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-07-16 DOI: 10.1002/med.70080

Rosalie Elvira, Qing Wang, Yun-Cheng Wu, Eng King Tan, Zhi Dong Zhou

{"title":"α-Synuclein Seeds Amplification Assays for Parkinson's Disease and Related Synucleinopathies","authors":"Rosalie Elvira, Qing Wang, Yun-Cheng Wu, Eng King Tan, Zhi Dong Zhou","doi":"10.1002/med.70080","DOIUrl":"10.1002/med.70080","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the pathological misfolding and aggregation of α-synuclein (α-syn), which leads to dopaminergic neuronal loss and multisystem dysfunction. Conventional clinical diagnosis is often delayed until after substantial neuronal degeneration has occurred. Recent advances in α-syn seed amplification assays (α-syn SAAs), including real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), have revolutionized PD biomarker research. These assays exploit the prion-like seeding and propagation properties of pathological α-syn to amplify trace aggregates in biological samples with exceptional sensitivity and specificity. Here, we summarize the mechanistic principles and biophysical underpinnings of α-syn SAAs, compare their diagnostic performance across biospecimens such as cerebrospinal fluid, skin, blood, and saliva, and evaluate their potential for differential diagnosis among synucleinopathies. We further discuss the integration of SAAs with other biomarkers including α-syn oligomer ELISAs, neurofilament light chain assays, and dopaminergic PET/SPECT imaging. Emerging developments, such as same-day RT-QuIC, quantitative kinetic readouts, and peripheral blood-based assays, are accelerating clinical translation. Despite challenges in assay standardization, strain discrimination, and regulatory validation, α-syn SAAs hold transformative potential for early diagnosis, patient stratification, and monitoring of therapeutic efficacy in PD. Their convergence with artificial intelligence, organoid modeling, and multimodal biomarker frameworks promises to redefine precision medicine in PD and other synucleinopathies.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1922-1938"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467949","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}

引用次数: 0

Phosphonates as Modulators of Brain Chemistry 磷酸盐作为脑化学调节剂。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-06-14 DOI: 10.1002/med.70070

Susana Santos Braga, Nádia E. Santos, Maria Almeida-Santos, Flávio F. Figueira, Filipe A. Almeida Paz

{"title":"Phosphonates as Modulators of Brain Chemistry","authors":"Susana Santos Braga, Nádia E. Santos, Maria Almeida-Santos, Flávio F. Figueira, Filipe A. Almeida Paz","doi":"10.1002/med.70070","DOIUrl":"10.1002/med.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>The present review describes the current knowledge on phosphonates designed for brain disease therapeutics, a less explored aspect of the studies on their medicinal chemistry. Because of their structural similarity with phosphates and of the ubiquitous presence of phosphate-dependent processes in the brain, phosphonate compounds are able to influence brain chemistry, interfering with neurotransmission and phosphorous-dependent bioprocesses. One of the main applications for phosphonates in the brain is Alzheimer's disease, for which they can be new drug candidates and/or afford innovative strategies for diagnostics. Such applications are described in the first section of this review, which includes a large number of reports on phosphonates with cholinesterase-inhibiting activity, some recent studies exploring phosphonates for inhibiting the interaction between amyloid-β protein and alcohol dehydrogenases, and phosphonate-based materials used in proteomics-based investigative and diagnosis platforms for the different stages of development of Alzheimer's disease. The second section of the review is dedicated to ischemic brain injury and to the development of phosphonates for active against NMDA and AMPA receptors with the purpose of reducing brain damage caused by glutamate excitotoxicity. Furthermore, agonists targeting the mGlu-4 receptor suggest potential for promoting neuroregeneration. The review concludes by emphasizing the relevance of phosphonate stability, versatility, and ability to mimic natural phosphate groups in the development of new therapeutic agents for brain disorders, weighing the advantages against the gaps in knowledge in order to set future directions of research in brain health.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1717-1734"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248375","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}

引用次数: 0

Plasmepsins as Antimalarial Drug Targets—Then, Now, and the Future 血浆蛋白酶作为抗疟疾药物靶点——过去、现在和未来。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-06-02 DOI: 10.1002/med.70065

Brad E. Sleebs

引用次数: 0

Molecular Pharmacology of T-Type Calcium Channels and Their Roles in Neurological Disorders t型钙通道的分子药理学及其在神经系统疾病中的作用。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-06-10 DOI: 10.1002/med.70068

Muhammad Umair, Laurent Ferron, Raja Hussain Ali, Gerald W. Zamponi, Yasinalli Tamboli

{"title":"Molecular Pharmacology of T-Type Calcium Channels and Their Roles in Neurological Disorders","authors":"Muhammad Umair, Laurent Ferron, Raja Hussain Ali, Gerald W. Zamponi, Yasinalli Tamboli","doi":"10.1002/med.70068","DOIUrl":"10.1002/med.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>Voltage-gated ion channels play important physiological roles by regulating the electrical activity of a range of different cell types through maintaining the gradients of different ions. Among these, voltage-gated calcium channels mediate various cellular activities, including muscle contraction, gene regulation, and neurotransmission. A sub-type of calcium channels are T-type calcium channels that play a critical role in regulating neuronal excitability and are essential for neurodevelopment. Mutations in genes encoding T-type calcium channels, including <i>CACNA1G</i>, <i>CACNA1H</i>, and <i>CACNA1I</i> can lead to altered channel activity, resulting in disrupted calcium entry, calcium signaling, synaptic plasticity, and neuronal differentiation. They have been implicated in a range of neurodevelopmental disorders, such as epilepsy, autism spectrum disorder, and intellectual disability. There has been considerable interest in developing blockers against T-type calcium channels to restore the dysregulated calcium homeostasis in neuronal disorders. T-type calcium channel blockers, originally developed for cardiovascular diseases, have emerged as potential therapeutic agents for neurodevelopmental disorders by targeting aberrant calcium signaling. This review explores the molecular mechanisms underlying T-type channel dysfunction caused by genetic mutations and evaluates the current evidence on the therapeutic efficacy of T-type calcium channel blockers in neurodevelopmental disorders. Although preclinical studies show promise, translating these findings into effective clinical therapies presents significant challenges. Future research focusing on optimizing blocker specificity and understanding the broader impact of channel modulation is necessary for developing targeted treatments for neurological pathologies.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1649-1671"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215889","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}

引用次数: 0

Decoding the Toxicity of Synthetic Cannabinoids: From Receptor Activation to Multiorgan Dysfunction 解码合成大麻素的毒性：从受体激活到多器官功能障碍。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-06-24 DOI: 10.1002/med.70073

Weihao Fan, Zhipeng Che, Li Xiao, Kaiting Shi, Qichao Meng, Lin Yang, Yao Lin, Yi Ye, Ying Wei, Linchuan Liao

{"title":"Decoding the Toxicity of Synthetic Cannabinoids: From Receptor Activation to Multiorgan Dysfunction","authors":"Weihao Fan, Zhipeng Che, Li Xiao, Kaiting Shi, Qichao Meng, Lin Yang, Yao Lin, Yi Ye, Ying Wei, Linchuan Liao","doi":"10.1002/med.70073","DOIUrl":"10.1002/med.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Synthetic cannabinoids (SCBs) represent a rapidly expanding and chemically diverse class of new psychoactive substances, deliberately designed to mimic the effects of natural cannabis. However, their high potency and full agonism at cannabinoid receptors lead to severe public health risks. The primary mechanism of SCBs' action involves the robust activation of CB1 and CB2 receptors, which in turn trigger a cascade of downstream events. This includes the profound dysregulation of key neurotransmitter systems, critical ion channel functions, and essential intracellular signaling pathways, culminating in widespread cellular dysfunction and damage. This comprehensive review delves into the multifaceted pathogenesis through which SCBs induce systemic harm. It systematically examines the clinical evidence and molecular mechanisms that connect SCB exposure to a spectrum of adverse outcomes, including life-threatening cardiovascular toxicities, significant neurological and psychiatric disorders, respiratory system diseases, digestive system diseases, and nephrotoxicity, and so forth. The point of this review, elucidating the intricate mechanisms underlying SCB toxicity, will be crucial, as this knowledge is the key to unlocking targeted therapies and effectively mitigating the severe health consequences of their abuse.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 6","pages":"1824-1870"},"PeriodicalIF":13.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306404","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}

引用次数: 0

Synthesis and Clinical Application of Small-Molecule Drugs Approved by FDA in 2025 2025年获FDA批准的小分子药物的合成与临床应用

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-05 Epub Date: 2026-05-25 DOI: 10.1002/med.70064

Liang Chang, Min Wang, Huijie Zhang, Zhen Li, Zixuan Song, Lijie Zhao, Fengli Jiang, Jiao Wang, Yuan Quan

引用次数: 0

The Executioners of Mitochondrial Apoptosis: Structures, Mechanisms, and Therapeutic Advances of BAX, BAK, and BOK. 线粒体凋亡的刽子手：BAX、BAK和BOK的结构、机制和治疗进展。

IF 13.6 1区医学

Medicinal Research Reviews Pub Date : 2026-10-03 DOI: 10.1002/med.70108

Hudie Wei, Jiaqi Wang, Jiayan Jiang, Shuyan Dai

引用次数: 0