Medicinal Research Reviews最新文献

Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery. 组蛋白去乙酰化酶与蛋白质降解：加速抗癌药物的发现。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-05-08 DOI: 10.1002/med.70052

Jun-Jie Wang, Ya Gao, Xin-Qian Ji, Jia-Yi Yin, Meng-Zhi Zhang, Bo Wang, Hui-Min Liu, Siqi Feng, Ning Wang, Guo-Liang Lu, Yan Li, Piet Herdewijn, Yi-Chao Zheng, Peng Yan, Xing-Jie Dai

{"title":"Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery.","authors":"Jun-Jie Wang, Ya Gao, Xin-Qian Ji, Jia-Yi Yin, Meng-Zhi Zhang, Bo Wang, Hui-Min Liu, Siqi Feng, Ning Wang, Guo-Liang Lu, Yan Li, Piet Herdewijn, Yi-Chao Zheng, Peng Yan, Xing-Jie Dai","doi":"10.1002/med.70052","DOIUrl":"https://doi.org/10.1002/med.70052","url":null,"abstract":"<p><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>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-08","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}

引用次数: 0

Advances in SIRT2-Targeted Therapeutics: Structural Insights, Chemical Strategies, and Degrader Technologies. sirt2靶向治疗的进展：结构见解、化学策略和降解技术。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-05-05 DOI: 10.1002/med.70054

Ahmed A Al-Karmalawy, Wolfgang Sippl, Abdullah Al-Dakhil, Tarek A Yousef, Arwa Omar Al Khatib, Samia S Hawas

{"title":"Advances in SIRT2-Targeted Therapeutics: Structural Insights, Chemical Strategies, and Degrader Technologies.","authors":"Ahmed A Al-Karmalawy, Wolfgang Sippl, Abdullah Al-Dakhil, Tarek A Yousef, Arwa Omar Al Khatib, Samia S Hawas","doi":"10.1002/med.70054","DOIUrl":"https://doi.org/10.1002/med.70054","url":null,"abstract":"<p><p>Sirtuin 2 (SIRT2) is an NAD⁺-dependent lysine deacylase that is a member of the sirtuin enzyme family and plays essential roles in cytoskeletal regulation, chromatin remodeling, metabolic control, inflammation, neurodegeneration, and cancer progression. Its diverse biological functions have positioned SIRT2 as a compelling but challenging therapeutic target. This review provides an integrated overview of recent advances in SIRT2 structural biology, emphasizing the catalytic core, substrate-binding channel, and the inducible selectivity pocket that enables isoform discrimination. We summarize the medicinal chemistry landscape of classical SIRT2 inhibitors, highlighting major scaffolds and determinants of potency and selectivity. Emerging strategies based on targeted protein degradation-including SirReal-derived PROTACs, hydrophobic-tag degraders, and non-CRBN E3 ligase systems-are discussed in comparison with traditional occupancy-driven inhibition, underscoring the advantages of event-driven degradation for eliminating both catalytic and non-catalytic SIRT2 functions. Drug repurposing efforts and computational screening approaches further expand the repertoire of potential SIRT2 modulators. Finally, we outline current challenges and future directions, including the need for improved selectivity, better pharmacokinetic profiles, deeper mechanistic understanding, and development of chemical probes for underexplored sirtuin isoforms. Together, these advances highlight the rapidly evolving landscape of SIRT2-targeted therapeutics and their emerging potential in oncology, neurodegeneration, and metabolic disease.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831628","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

Multi-Targeting Ligands as Prospective Therapeutics for Alzheimer's Disease, a Prevalent Neurodegenerative Disorder: Mechanistic Insights, Emerging Targets and Drug Discovery Campaigns. 多靶向配体作为阿尔茨海默病（一种普遍的神经退行性疾病）的前瞻性治疗方法：机制见解、新靶点和药物发现活动。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-19 DOI: 10.1002/med.70047

Amandeep Thakur, Mandeep Rana, Sakshi Vanjani, Kei-Chi Liou, Rajeev Taliyan, Kunal Nepali, Chih-Hao Yang

{"title":"Multi-Targeting Ligands as Prospective Therapeutics for Alzheimer's Disease, a Prevalent Neurodegenerative Disorder: Mechanistic Insights, Emerging Targets and Drug Discovery Campaigns.","authors":"Amandeep Thakur, Mandeep Rana, Sakshi Vanjani, Kei-Chi Liou, Rajeev Taliyan, Kunal Nepali, Chih-Hao Yang","doi":"10.1002/med.70047","DOIUrl":"https://doi.org/10.1002/med.70047","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a debilitating neurodegenerative condition characterized by progressive cognitive impairment, memory deterioration, and neuronal dysfunction. Its complex pathophysiology involves multiple interlinked processes, including amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, synaptic dysfunction, and cholinergic deficits. Current FDA-approved therapies provide only symptomatic relief and fail to halt disease progression, highlighting the urgent need for more effective treatment strategies. This review provides a comprehensive overview of the pathological mechanisms underlying AD and the emerging therapeutic targets for the design of tractable anti-AD scaffolds, namely, acetylcholinesterase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), glycogen synthase kinase-3β (GSK3β), dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), histone deacetylases (HDACs), and soluble epoxide hydrolase (sEH). Emphasis is placed on the paradigm shift from single-target therapies to multitarget-directed ligands (MTDLs), which are increasingly recognized as promising tools to tackle AD's multifactorial pathology. We also discuss recent advances in medicinal chemistry and structure-guided drug discovery campaigns aimed at developing pharmacologically optimized, BBB-penetrant MTDLs. By consolidating mechanistic insights with therapeutic innovation, this review aims to facilitate the development of next-generation therapeutics with enhanced efficacy and disease-modifying potential in AD.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715343","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

Respiratory Syncytial Virus (RSV): A Comprehensive Overview From Basic Biology to Clinical Prevention and Control 呼吸道合胞病毒（RSV）：从基础生物学到临床防治的综合综述。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 Epub Date: 2025-11-19 DOI: 10.1002/med.70025

Jie Shi, Xiya Huang, Chunjun Ye, Yishan Lu, Yanyan Liu, Yuquan Wei, Xiawei Wei

{"title":"Respiratory Syncytial Virus (RSV): A Comprehensive Overview From Basic Biology to Clinical Prevention and Control","authors":"Jie Shi, Xiya Huang, Chunjun Ye, Yishan Lu, Yanyan Liu, Yuquan Wei, 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}

引用次数: 0

Front Cover Image, Volume 46, Issue 3 封面图像，第46卷，第3期

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 DOI: 10.1002/med.70044

Jiayi Deng, Yasi Deng, Yuxin Chen, Fan Bai, Bowen Zhang, Wuyang Jiang, Wei Wang, Huanghe Yu

引用次数: 0

FDA-Approved Pyrimidine-Containing Drugs: Synthesis and Clinical Application fda批准的含嘧啶药物：合成和临床应用。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 Epub Date: 2025-11-20 DOI: 10.1002/med.70027

Yao Zhang, Xiaomei Liu, Chong Zhang, Yanke Li, Guangzhe Zhang, Zhenhua Du

引用次数: 0

The Potential, Challenges and New Horizons of Marine Natural Products Against Tuberculosis Infection 海洋天然产物抗结核感染的潜力、挑战和新前景。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 Epub Date: 2025-12-07 DOI: 10.1002/med.70028

Qun Zhang, Yi-Qian Han, Wei-Feng Xu, Mei-Yan Wei, Yu-Cheng Gu, Chang-Lun Shao

{"title":"The Potential, Challenges and New Horizons of Marine Natural Products Against Tuberculosis Infection","authors":"Qun Zhang, Yi-Qian Han, Wei-Feng Xu, Mei-Yan Wei, Yu-Cheng Gu, Chang-Lun Shao","doi":"10.1002/med.70028","DOIUrl":"10.1002/med.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Tuberculosis (TB) is one of the most significant health perils that has claimed more lives than any other contagious disease over the past 2000 years. The treatment of tuberculosis has been severely compromised due to drug-resistant strains. In this review, we cover the field of the clinical pipeline of tuberculosis drugs, and summarize the progress of their targets and structures. A wide range of marine natural products (MNPs) with novel structures and remarkable activities have potential for the development of antituberculosis drugs. We systematically summarize the progress and potential of 107 potent MNPs that have shown activity against tuberculosis infection. Additionally, we highlight the physicochemical properties of MNPs, total synthesis, and biosynthesis of bioactive compounds, to further evaluate their drug-likeness and sustainability of compound supply. However, the intricate nature of the pathogen, drug misuse, bottlenecks in the supply of MNPs, and other problems pose challenges to reaching the goal of completely eradicating tuberculosis worldwide. Reliable alternative models, screening based on enzyme activity, and combination therapies may be transforming discovery and application in the field of antituberculosis drugs, accelerating discovery and improving sustainable therapeutic effects. These promising lead compounds and widely emerging technologies broaden horizons for developing marine drugs.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 3","pages":"774-802"},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699412","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

The IL-23/IL-17/NF-κB Signaling Pathway in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Agents 类风湿关节炎中的IL-23/IL-17/NF-κB信号通路：分子机制和治疗药物。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 Epub Date: 2025-11-16 DOI: 10.1002/med.70024

Jiayi Deng, Yasi Deng, Yuxin Chen, Fan Bai, Bowen Zhang, Wuyang Jiang, Wei Wang, Huanghe Yu

{"title":"The IL-23/IL-17/NF-κB Signaling Pathway in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Agents","authors":"Jiayi Deng, Yasi Deng, Yuxin Chen, Fan Bai, Bowen Zhang, Wuyang Jiang, Wei Wang, Huanghe Yu","doi":"10.1002/med.70024","DOIUrl":"10.1002/med.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joint synovium, which can lead to bone destruction. Prolonged inadequate treatment can result in joint disability and an increased risk of mortality. Currently, there are considerable limitations in the availability of effective therapeutic agents for RA. The IL-23/IL-17/NF-κB signaling pathway has emerged as a central pathogenic mechanism underlying the multistage development of RA. This pathway initiates the initial inflammatory response, driving excessive proliferation of the synovial tissue, ultimately leading to late-stage bone and cartilage destruction. A comprehensive understanding of the role of the IL-23/IL-17/NF-κB pathway in the pathogenesis of RA can facilitate the refinement of scientific understanding of RA pathogenesis and assist in developing new therapeutic regimens. A comprehensive literature review and data search were conducted in several scientific databases, including Web of Science, PubMed, Google Scholar, Embase, TCMSP, PubChem, Swiss ADME, and Swiss Target Prediction. The literature review was conducted from 2013 to 2025. The search terms employed included RA, IL-23, IL-17, NF-κB, molecular mechanisms, and therapeutic agents. Following a rigorous screening process, irrelevant data were excluded, resulting in a focused analysis and comprehensive review of the key role of the IL-23/IL-17/NF-κB signaling axis in the multifaceted pathogenesis of RA and the key active ingredients and possible targets of action of related drugs. This comprehensive literature review aims to provide novel mechanistic insights and valuable references to guide the development of more effective therapeutic strategies for this debilitating autoimmune disease.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 3","pages":"625-671"},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533944","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

Kinin B1 and B2 Receptors: Role in Tumor Progression and Pain Associated With Tumor and Anticancer Therapy 激肽B1和B2受体：与肿瘤和抗癌治疗相关的肿瘤进展和疼痛的作用。

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 Epub Date: 2025-11-11 DOI: 10.1002/med.70019

Indiara Brusco, Sara Marchesan Oliveira

{"title":"Kinin B1 and B2 Receptors: Role in Tumor Progression and Pain Associated With Tumor and Anticancer Therapy","authors":"Indiara Brusco, Sara Marchesan Oliveira","doi":"10.1002/med.70019","DOIUrl":"10.1002/med.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer is the second leading cause of death globally, with an estimated worldwide incidence of 19.3 million cases in 2020, and is expected to increase by 47% in the next 20 years. Painful symptoms of tumors and anticancer treatment negatively impact the quality of life of patients with cancer. Cancer pain can occur during all disease periods, being more debilitating and hardest to treat, mainly when tumors metastasize to the bone. Common tumors such as breast, lung, and prostate often metastasize to the bones and cause severe pain in patients. Anticancer therapy with some chemotherapy and hormonal drugs also induces painful symptoms, compromising antineoplastic treatment. Among the analgesics recommended to treat cancer pain, NSAIDs and paracetamol seem to have predominantly antiproliferative activity. However, opioids, mainly morphine, present conflicting effects in reducing and promoting tumor progression. Kinins and their B<sub>1</sub> and B<sub>2</sub> receptors contribute to the development of numerous painful symptoms,including those induced by tumors and anticancer therapy. In addition, kinins stimulate the proliferation of various tumors (breast, lung, prostate and others) while having controversial effects in melanoma. Thus, kinin B<sub>1</sub> and B<sub>2</sub> receptors could be a promising pharmacological target to treat the pain caused by the tumor and its therapy while reducing tumor proliferation. However, it is essential to review the effects of kinins in each specific type of cancer to investigate their involvement in pain. This assessment is also valid and prudent for new analgesic candidates against cancer pain and their therapy, especially to rule out a possible pro-tumor activity of this analgesic.</p>\u0000 </div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 3","pages":"585-624"},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494038","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

Medicinal Chemistry Strategies for the Development of CD73 Inhibitors in Cancer Immunotherapy 肿瘤免疫治疗中CD73抑制剂开发的药物化学策略

IF 11.6 1区医学

Medicinal Research Reviews Pub Date : 2026-04-08 Epub Date: 2025-12-04 DOI: 10.1002/med.70029

Meng Cui, Shaowei Ma, Zhe Huang, Danye Zhang, Xiaofei Sun, Yue You

{"title":"Medicinal Chemistry Strategies for the Development of CD73 Inhibitors in Cancer Immunotherapy","authors":"Meng Cui, Shaowei Ma, Zhe Huang, Danye Zhang, Xiaofei Sun, Yue You","doi":"10.1002/med.70029","DOIUrl":"10.1002/med.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>CD73, a membrane-bound ecto-5′-nucleotidase, catalyzes the extracellular conversion of adenosine monophosphate into immunosuppressive adenosine. Functioning as an emerging immune checkpoint, CD73 is frequently upregulated across numerous tumor types, contributing to the accumulation of adenosine within the tumor microenvironment and promoting immune evasion. Intensive efforts have led to the discovery of diverse CD73 inhibitors, which show strong potential in cancer immunotherapy. To date, around eighteen candidates targeting CD73 have entered clinical evaluation, many exhibiting encouraging efficacy in combination regimens for solid tumors. This review provides an overview of the biological functions of CD73 in tumor-induced immunosuppression and highlights the medicinal chemistry strategies employed in the development of small-molecule CD73 inhibitors since 2018. Additionally, the challenges in drug design and future directions are also discussed to enhance the clinical applicability of CD73-targeted therapies in cancer treatment. We believe that this review will offer valuable insights to guide the rational design of next-generation CD73 inhibitors for cancer immunotherapy.</p></div>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"46 3","pages":"749-773"},"PeriodicalIF":11.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676042","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