Medicinal Research Reviews最新文献

Recent Progress in Azobenzene-Based In Vivo Photopharmacology. 偶氮苯类体内光药理学研究进展。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-05-26 DOI: 10.1002/med.22120

Xin Zhou, Lupei Du, Minyong Li

{"title":"Recent Progress in Azobenzene-Based In Vivo Photopharmacology.","authors":"Xin Zhou, Lupei Du, Minyong Li","doi":"10.1002/med.22120","DOIUrl":"https://doi.org/10.1002/med.22120","url":null,"abstract":"As the most extensively studied photoswitch in photopharmacology, the azobenzene photoswitch has precision instrumental in the photoregulation of physiological processes across various animal models. Currently, it exhibits the greatest clinical potential for photosensitive retinal restoration, capable of inducing long-term therapeutic effects following intravitreal injection, without the need for foreign gene expression or optical fiber implantation. A significant advancement in the application of azobenzene photoswitches is their integration with optical flow control technology, which facilitates the targeting of deep tissues within the mouse cerebral cortex, addressing long-standing challenges related to tissue penetration depth in photopharmacology. With exceptional spatial and temporal resolution, photopharmacology is particularly well-suited for precision medicine, holding substantial potential for further development. Consequently, a comprehensive summary and review of the design strategies of azobenzene photoswitches for In Vivo applications, along with their experimental outcomes, are essential for guiding future advancements in photopharmacology. This review provides an overview of the fundamental properties and design strategies of azobenzene photoswitch molecules. Additionally, we extensively summarize all azobenzene photoswitch molecules successfully applied In Vivo for photopharmacological purposes since 2006, covering species such as Caenorhabditis elegans, Xenopus tadpoles, zebrafish, mice, rats, rabbits, and canines. Finally, we discuss the challenges associated with the In Vivo implementation of azobenzene photoswitch molecules and propose potential solutions.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148803","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

Therapeutic Potential of Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO) Inhibitors: Current Medicinal Chemistry and Emerging Opportunities. 血管粘附蛋白-1 (VAP-1)/氨基脲敏感胺氧化酶（SSAO）抑制剂的治疗潜力：当前药物化学和新兴机会

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-05-21 DOI: 10.1002/med.22118

Pinaki Bhattacharjee, Malliga R Iyer

{"title":"Therapeutic Potential of Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO) Inhibitors: Current Medicinal Chemistry and Emerging Opportunities.","authors":"Pinaki Bhattacharjee, Malliga R Iyer","doi":"10.1002/med.22118","DOIUrl":"https://doi.org/10.1002/med.22118","url":null,"abstract":"Semicarbazide-sensitive amine oxidase (SSAO) is a vascular enzyme and expressed in high concentrations in vascular smooth muscle cells (VSMCs), localized in the caveolae of the plasma membrane, and the endothelial cells. SSAO is classified as a copper amine oxidase and encoded by the amine oxidase copper-containing 3 gene. SSAO exists both as a soluble protein and as a tissue-bound transmembrane protein. The latter is often called vascular adhesion protein 1. Vascular adhesion protein-1 or VAP-1, encoded by the AOC3 gene, is a pro-inflammatory and multifunctional molecule belonging to the SSAO family. It assists the transformation of primary amines to aldehydes resulting in the production of hydrogen peroxide and ammonia. Work from the last two decades, has shown that VAP-1/SSAO plays a role in several physiological and pathological processes, making it a potentially valuable target for therapeutic development. In this review, we provide a detailed overview of the inhibitors of VAP-1/SSAO that are being developed specifically for the treatment of inflammatory diseases. Here in we have highlighted important aspects of the compounds investigated in therapeutic applications. Furthermore, we have outlined potential avenues for innovation with the aim of maximizing the therapeutic efficacy of VAP-1/SSAO inhibitors in clinical settings.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109101","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

Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders. 靶向组蛋白H3K9甲基转移酶G9a作为神经精神疾病的潜在治疗策略

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-05-19 DOI: 10.1002/med.22119

Malak Hajar, Tobias Werner, Mihajlo Gajic, Holger Stark, Bassem Sadek

引用次数: 0

The Therapeutic Potential of Melatonin and Its Novel Synthetic Analogs in Circadian Rhythm Sleep Disorders, Inflammation-Associated Pathologies, and Neurodegenerative Diseases. 褪黑素及其新型合成类似物在昼夜节律睡眠障碍、炎症相关病理和神经退行性疾病中的治疗潜力

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-05-08 DOI: 10.1002/med.22117

Rodrigo F N Ribeiro, Marco Rios Santos, Maria Aquino, Luis Pereira de Almeida, Cláudia Cavadas, Maria Manuel C Silva

{"title":"The Therapeutic Potential of Melatonin and Its Novel Synthetic Analogs in Circadian Rhythm Sleep Disorders, Inflammation-Associated Pathologies, and Neurodegenerative Diseases.","authors":"Rodrigo F N Ribeiro, Marco Rios Santos, Maria Aquino, Luis Pereira de Almeida, Cláudia Cavadas, Maria Manuel C Silva","doi":"10.1002/med.22117","DOIUrl":"https://doi.org/10.1002/med.22117","url":null,"abstract":"Melatonin, N-acetyl-5-methoxytryptamine, is a tryptophan-derived hormone mostly produced in the pineal gland, despite being synthesized locally at several tissues and organs. This production is rhythmically controlled by complex clock gene networks in the master pacemaker located in the suprachiasmatic nucleus of the hypothalamus. Melatonin is usually secreted only during the dark phase of the day and is essential to synchronize circadian rhythms and neuroendocrine physiological processes. Its main clinical use is associated with the treatment of jet lag and other circadian rhythm sleep disorders, with a growing number of other promising therapeutic applications due to the diverse physiological roles of melatonin. In this review, we explore melatonin and its receptors and provide an updated overview on research concerning the role of melatonin, either as an endogenous molecule or as a drug, in: sleep-wake cycle regulation; circadian rhythms; inflammatory processes that may compromise cardiovascular, respiratory, gastrointestinal, renal, and reproductive system functions; and neurodegenerative disorders such as Alzheimer's and Parkinson's disease. The most recent and promising research findings concerning melatonin synthetic analogs such as agomelatine and ramelteon are highlighted, pointing toward new compounds with promising pharmacological activity while emphasizing their structural differences and advantages when compared to melatonin.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964675","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

Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide. 令人信服的证据：一氧化碳治疗潜力的关键更新。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-04-30 DOI: 10.1002/med.22116

Nicola Bauer, Qiyue Mao, Aditi Vashistha, Anupamaa Seshadri, Yi-Chieh Nancy Du, Leo Otterbein, Chalet Tan, Mark P de Caestecker, Binghe Wang

{"title":"Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide.","authors":"Nicola Bauer, Qiyue Mao, Aditi Vashistha, Anupamaa Seshadri, Yi-Chieh Nancy Du, Leo Otterbein, Chalet Tan, Mark P de Caestecker, Binghe Wang","doi":"10.1002/med.22116","DOIUrl":"https://doi.org/10.1002/med.22116","url":null,"abstract":"Carbon monoxide (CO) is an endogenous signaling molecule. It is produced via heme degradation by heme oxygenase (HMOX), releasing stoichiometric amounts of CO, iron, and biliverdin (then bilirubin). The HMOX-CO axis has long been shown to offer beneficial effects by modulating inflammation, proliferation and cell death as they relate to tissue and organ protection. Recent years have seen a large number of studies examining CO pharmacology, its molecular targets, cellular mechanisms of action, pharmacokinetics, and detection methods using various delivery modalities including inhaled CO gas, CO solutions, and various types of CO donors. Unfortunately, one widely used donor type includes four commercially available carbonyl complexes with metal or borane, CORM-2 (Ru2+), CORM-3 (Ru2+), CORM-A1 (BH3), and CORM-401 (Mn+), which have been shown to have minimal and/or unpredictable CO production and extensive CO-independent chemical reactivity and biological activity. As a result, not all \"CO biological activities\" in the literature can be attributed to CO. In this review, we summarize key findings based on CO gas and CO in solution for the certainty of the active principal and to avoid data contamination resulting from the confirmed or potential reactivities and activities of the \"carrier\" portion of CORMs. Along a similar line, we discuss interesting potential research areas of CO in the brain including a newly proposed CO/HMOX/dopamine axis and the role of CO in cognitive stimulation and circadian rhythm. This review is critical for the future development of the CO field by steering clear of complications caused by chemically reactive donor molecules.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951727","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

Harnessing the Power of Natural Products for Targeted Protein Degradation. 利用天然产物的力量进行靶向蛋白质降解。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-04-30 DOI: 10.1002/med.22113

Bo Zhu, Zheng Wu, Yiwen Shou, Kaili Zhao, Qinpei Lu, Jiang-Jiang Qin, Hongwei Guo

{"title":"Harnessing the Power of Natural Products for Targeted Protein Degradation.","authors":"Bo Zhu, Zheng Wu, Yiwen Shou, Kaili Zhao, Qinpei Lu, Jiang-Jiang Qin, Hongwei Guo","doi":"10.1002/med.22113","DOIUrl":"https://doi.org/10.1002/med.22113","url":null,"abstract":"Natural products have garnered significant attention due to their complex chemical structures and remarkable pharmacological activities. With inherent recognition capabilities for protein surfaces, natural products serve as ideal candidates for designing proteolysis-targeting chimeras (PROTACs). The utilization of natural products in PROTAC development offers distinct advantages, including their rich chemical diversity, multitarget activities, and sustainable sourcing. This comprehensive review explores the vast potential of harnessing natural products in PROTAC research. Moreover, the review discusses the application of natural degradant technology, which involves utilizing natural product-based compounds to selectively degrade disease-causing proteins, as well as the implementation of computer-aided drug design (CADD) technology in identifying suitable targets for degradation within the realm of natural products. By harnessing the power of natural products and leveraging computational tools, PROTACs derived from natural products have the potential to revolutionize drug discovery and provide innovative therapeutic interventions for various diseases.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956937","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 Hsp90β Isoform: An Attractive Target for Drug Development. Hsp90β亚型：一个有吸引力的药物开发靶点

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-04-28 DOI: 10.1002/med.22114

Subhabrata Chaudhury, Terin D'Amico, Brian S J Blagg

引用次数: 0

The Quinoline Photoremovable Group (PPG) Platform-A Medicinal Chemist's Approach for Photocage Development and Applications. 喹啉光移除基（PPG）平台——药物化学家的光笼开发和应用方法。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-04-12 DOI: 10.1002/med.22111

Bence Kontra, Zoltán Mucsi, Janez Ilaš, Petra Dunkel

{"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":"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.","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}

引用次数: 0

Molecular Tools to Study and Control Dopaminergic Neurotransmission With Light. 利用光研究和控制多巴胺能神经传递的分子工具。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-04-10 DOI: 10.1002/med.22112

Galyna Maleeva, Carlo Matera, Silvia Roda, Alessio Colleoni, Marco De Amici, Pau Gorostiza

{"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":"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.","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}

引用次数: 0

Marine Natural Products in Inflammation-Related Diseases: Opportunities and Challenges. 海洋天然产物与炎症相关疾病：机遇与挑战。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-04-09 DOI: 10.1002/med.22109

Tao Zhang, Zijun Ouyang, Yueran Zhang, Haiyan Sun, Lingdong Kong, Qiang Xu, Jiao Qu, Yang Sun

引用次数: 0