Shuai-Jiang Liu, Qian Zhao, Xiao-Chen Liu, Allan B. Gamble, Wei Huang, Qian-Qian Yang, Bo Han
{"title":"Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery","authors":"Shuai-Jiang Liu, Qian Zhao, Xiao-Chen Liu, Allan B. Gamble, Wei Huang, Qian-Qian Yang, Bo Han","doi":"10.1002/med.22037","DOIUrl":"10.1002/med.22037","url":null,"abstract":"<p>Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 5","pages":"1971-2014"},"PeriodicalIF":10.9,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183297","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}
Mandeep Kaur, Salvatore Fusco, Bram Van den Broek, Jaya Aseervatham, Abdolmohamad Rostami, Lorraine Iacovitti, Claudio Grassi, Barbara Lukomska, Amit K. Srivastava
{"title":"Most recent advances and applications of extracellular vesicles in tackling neurological challenges","authors":"Mandeep Kaur, Salvatore Fusco, Bram Van den Broek, Jaya Aseervatham, Abdolmohamad Rostami, Lorraine Iacovitti, Claudio Grassi, Barbara Lukomska, Amit K. Srivastava","doi":"10.1002/med.22035","DOIUrl":"10.1002/med.22035","url":null,"abstract":"<p>Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood–brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use in the CNS. This review article aims to provide a comprehensive introduction to EVs, encompassing various aspects such as their diverse isolation methods, characterization, handling, storage, and different routes for EV administration. Additionally, it underscores the recent advances in their potential applications in neurodegenerative disorder therapeutics. By exploring their unique capabilities, this study sheds light on the promising future of EVs in clinical research. It considers the inherent challenges and limitations of these emerging applications while incorporating the most recent updates in the field.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1923-1966"},"PeriodicalIF":13.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157185","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}
Xiujiao Qin, Hongyuan Li, Huiying Zhao, Le Fang, Xiaohui Wang
{"title":"Enhancing healthy aging with small molecules: A mitochondrial perspective","authors":"Xiujiao Qin, Hongyuan Li, Huiying Zhao, Le Fang, Xiaohui Wang","doi":"10.1002/med.22034","DOIUrl":"10.1002/med.22034","url":null,"abstract":"<p>The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha-lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5′-monophosphate-activated protein kinase activators, and compounds like metformin and mitochondria-targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age-related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1904-1922"},"PeriodicalIF":13.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118328","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}
Jingya Li, Zhuoyuan Zhang, Jinru Tang, Zeyu Hou, Longjiang Li, Bo Li
{"title":"Emerging roles of nerve-bone axis in modulating skeletal system","authors":"Jingya Li, Zhuoyuan Zhang, Jinru Tang, Zeyu Hou, Longjiang Li, Bo Li","doi":"10.1002/med.22031","DOIUrl":"10.1002/med.22031","url":null,"abstract":"<p>Over the past decades, emerging evidence in the literature has demonstrated that the innervation of bone is a crucial modulator for skeletal physiology and pathophysiology. The nerve-bone axis sparked extensive preclinical and clinical investigations aimed at elucidating the contribution of nerve-bone crosstalks to skeleton metabolism, homeostasis, and injury repair through the perspective of skeletal neurobiology. To date, peripheral nerves have been widely reported to mediate bone growth and development and fracture healing via the secretion of neurotransmitters, neuropeptides, axon guidance factors, and neurotrophins. Relevant studies have further identified several critical neural pathways that stimulate profound alterations in bone cell biology, revealing a complex interplay between the skeleton and nerve systems. In addition, inspired by nerve-bone crosstalk, novel drug delivery systems and bioactive materials have been developed to emulate and facilitate the process of natural bone repair through neuromodulation, eventually boosting osteogenesis for ideal skeletal tissue regeneration. Overall, this work aims to review the novel research findings that contribute to deepening the current understanding of the nerve-bone axis, bringing forth some schemas that can be translated into the clinical scenario to highlight the critical roles of neuromodulation in the skeletal system.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1867-1903"},"PeriodicalIF":13.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139988795","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}
Roberta Solidoro, Antonella Centonze, Morena Miciaccia, Olga Maria Baldelli, Domenico Armenise, Savina Ferorelli, Maria Grazia Perrone, Antonio Scilimati
{"title":"Fluorescent imaging probes for in vivo ovarian cancer targeted detection and surgery","authors":"Roberta Solidoro, Antonella Centonze, Morena Miciaccia, Olga Maria Baldelli, Domenico Armenise, Savina Ferorelli, Maria Grazia Perrone, Antonio Scilimati","doi":"10.1002/med.22027","DOIUrl":"10.1002/med.22027","url":null,"abstract":"<p>Ovarian cancer is the most lethal gynecological cancer, with a survival rate of approximately 40% at five years from the diagno. The first-line treatment consists of cytoreductive surgery combined with chemotherapy (platinum- and taxane-based drugs). To date, the main prognostic factor is related to the complete surgical resection of tumor lesions, including occult micrometastases. The presence of minimal residual diseases not detected by visual inspection and palpation during surgery significantly increases the risk of disease relapse. Intraoperative fluorescence imaging systems have the potential to improve surgical outcomes. Fluorescent tracers administered to the patient may support surgeons for better real-time visualization of tumor lesions during cytoreductive procedures. In the last decade, consistent with the discovery of an increasing number of ovarian cancer-specific targets, a wide range of fluorescent agents were identified to be employed for intraoperatively detecting ovarian cancer. Here, we present a collection of fluorescent probes designed and developed for fluorescence-guided ovarian cancer surgery. Original articles published between 2011 and November 2022 focusing on fluorescent probes, currently under preclinical and clinical investigation, were searched in PubMed. The keywords used were <i>targeted detection, ovarian cancer, fluorescent probe, near-infrared fluorescence, fluorescence-guided surgery</i>, and <i>intraoperative imaging</i>. All identified papers were English-language full-text papers, and probes were classified based on the location of the biological target: intracellular, membrane, and extracellular.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1800-1866"},"PeriodicalIF":13.3,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139759606","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":"cGAS-STING pathway agonists are promising vaccine adjuvants","authors":"Xinyu Tian, Jiayuan Ai, Xiaohe Tian, Xiawei Wei","doi":"10.1002/med.22016","DOIUrl":"10.1002/med.22016","url":null,"abstract":"<p>Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long-lasting immunity. However, there are only a few adjuvants that have been approved for clinical use, which highlights the need for exploring and developing new adjuvants to meet the growing demand for vaccination. Recently, emerging evidence demonstrates that the cGAS-STING pathway orchestrates innate and adaptive immunity by generating type I interferon responses. Many cGAS-STING pathway agonists have been developed and tested in preclinical research for the treatment of cancer or infectious diseases with promising results. As adjuvants, cGAS-STING agonists have demonstrated their potential to activate robust defense immunity in various diseases, including COVID-19 infection. This review summarized the current developments in the field of cGAS-STING agonists with a special focus on the latest applications of cGAS-STING agonists as adjuvants in vaccination. Potential challenges were also discussed in the hope of sparking future research interests to further the development of cGAS-STING as vaccine adjuvants.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1768-1799"},"PeriodicalIF":13.3,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696589","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":"Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective","authors":"Xiujin Chang, Fangui Qu, Chunxiao Li, Jingtian Zhang, Yanqing Zhang, Yuanyuan Xie, Zhongpeng Fan, Jinlei Bian, Jubo Wang, Zhiyu Li, Xi Xu","doi":"10.1002/med.22024","DOIUrl":"10.1002/med.22024","url":null,"abstract":"<p>Unprecedented therapeutic targeting of previously undruggable proteins has now been achieved by molecular-glue-mediated proximity-induced degradation. As a small GTPase, G1 to S phase transition 1 (GSPT1) interacts with eRF1, the translation termination factor, to facilitate the process of translation termination. Studied demonstrated that GSPT1 plays a vital role in the acute myeloid leukemia (AML) and MYC-driven lung cancer. Thus, molecular glue (MG) degraders targeting GSPT1 is a novel and promising approach for treating AML and MYC-driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of GSPT1, highlighting the latest advances and challenges in MG degraders, as well as some representative patents. The structure-activity relationships, mechanism of action and pharmacokinetic features of MG degraders are emphasized to provide a comprehensive compendium on the rational design of GSPT1 MG degraders. We hope to provide an updated overview, and design guide for strategies targeting GSPT1 for the treatment of cancer.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1727-1767"},"PeriodicalIF":13.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690813","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}
Yu Zheng, Yuke Li, Mao Li, Rujing Wang, Yuhong Jiang, Mengnan Zhao, Jun Lu, Rui Li, Xiaofang Li, Sanjun Shi
{"title":"Inside Front Cover Image, Volume 44, Issue 2","authors":"Yu Zheng, Yuke Li, Mao Li, Rujing Wang, Yuhong Jiang, Mengnan Zhao, Jun Lu, Rui Li, Xiaofang Li, Sanjun Shi","doi":"10.1002/med.22029","DOIUrl":"https://doi.org/10.1002/med.22029","url":null,"abstract":"<p>The cover image is based on the Review Article <i>COVID-19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms</i> by Yu Zheng et al., https://doi.org/10.1002/med.21997\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":"44 2","pages":"ii"},"PeriodicalIF":13.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139695268","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}
Kang Wang, Yuecan Zhang, Guangji Wang, Haiping Hao, Hong Wang
{"title":"Front Cover Image, Volume 44, Issue 2","authors":"Kang Wang, Yuecan Zhang, Guangji Wang, Haiping Hao, Hong Wang","doi":"10.1002/med.22028","DOIUrl":"https://doi.org/10.1002/med.22028","url":null,"abstract":"<p>The cover image is based on the Review Article <i>FXR agonists for MASH therapy: Lessons and perspectives from obeticholic acid</i> by Kang Wang et al., https://doi.org/10.1002/med.21991\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":"44 2","pages":"i"},"PeriodicalIF":13.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139695267","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}
Dipesh S. Harmalkar, Aneesh Sivaraman, Hossam Nada, Joohan Lee, Hyeseul Kang, Yongseok Choi, Kyeong Lee
{"title":"Natural products as IL-6 inhibitors for inflammatory diseases: Synthetic and SAR perspective","authors":"Dipesh S. Harmalkar, Aneesh Sivaraman, Hossam Nada, Joohan Lee, Hyeseul Kang, Yongseok Choi, Kyeong Lee","doi":"10.1002/med.22022","DOIUrl":"10.1002/med.22022","url":null,"abstract":"<p>Interleukin-6 (IL-6), a pleiotropic cytokine, plays a pivotal role in the pathophysiology of various diseases including diabetes, atherosclerosis, Alzheimer's disease, multiple myeloma, rheumatoid arthritis, and prostate cancer. The signaling pathways associated with IL-6 offer promising targets for therapeutic interventions in inflammatory diseases and IL-6-dependent tumors. Although certain anti-IL-6 monoclonal antibodies are currently employed clinically, their usage is hampered by drawbacks such as high cost and potential immunogenicity, limiting their application. Thus, the imperative arises to develop novel small non-peptide molecules acting as IL-6 inhibitors. Various natural products derived from diverse sources have been investigated for their potential to inhibit IL-6 activity. Nevertheless, these natural products remain inadequately explored in terms of their structure-activity relationships. In response, our review aims to provide syntheses and structure activity perspective of natural IL-6 inhibitors. The comprehensive amalgamation of information presented in this review holds the potential to serve as a foundation for forthcoming research endeavors by medicinal chemists, facilitating the design of innovative IL-6 inhibitors to address the complexities of inflammatory diseases.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 4","pages":"1683-1726"},"PeriodicalIF":13.3,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663931","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}