Medicinal Research Reviews最新文献

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A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection. 全面概述 microRNA 与病毒发病和感染之间的相互关系。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-26 DOI: 10.1002/med.22073
Seyedeh Zahra Bahojb Mahdavi, Asiyeh Jebelli, Parisa Shiri Aghbash, Behzad Baradaran, Mohammad Amini, Fatemeh Oroojalian, Nasser Pouladi, Hossein Bannazadeh Baghi, Miguel de la Guardia, Amir Ali Mokhtarzadeh
{"title":"A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection.","authors":"Seyedeh Zahra Bahojb Mahdavi, Asiyeh Jebelli, Parisa Shiri Aghbash, Behzad Baradaran, Mohammad Amini, Fatemeh Oroojalian, Nasser Pouladi, Hossein Bannazadeh Baghi, Miguel de la Guardia, Amir Ali Mokhtarzadeh","doi":"10.1002/med.22073","DOIUrl":"https://doi.org/10.1002/med.22073","url":null,"abstract":"<p><p>Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054396","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
Deciphering the enigmas of non-nucleoside reverse transcriptase inhibitors (NNRTIs): A medicinal chemistry expedition towards combating HIV drug resistance. 破解非核苷类逆转录酶抑制剂(NNRTIs)之谜:对抗艾滋病抗药性的药物化学探险。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-26 DOI: 10.1002/med.22080
Kun Zhang, Yu-Jie Zhang, Min Li, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
{"title":"Deciphering the enigmas of non-nucleoside reverse transcriptase inhibitors (NNRTIs): A medicinal chemistry expedition towards combating HIV drug resistance.","authors":"Kun Zhang, Yu-Jie Zhang, Min Li, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen","doi":"10.1002/med.22080","DOIUrl":"https://doi.org/10.1002/med.22080","url":null,"abstract":"<p><p>The pivotal involvement of reverse transcriptase activity in the pathogenesis of the progressive HIV virus has stimulated gradual advancements in drug discovery initiatives spanning three decades. Consequently, nonnucleoside reverse transcriptase inhibitors (NNRTIs) have emerged as a preeminent category of therapeutic agents for HIV management. Academic institutions and pharmaceutical companies have developed numerous NNRTIs, an essential component of antiretroviral therapy. Six NNRTIs have received Food and Drug Administration approval and are widely used in clinical practice, significantly improving the quality of HIV patients. However, the rapid emergence of drug resistance has limited the effectiveness of these medications, underscoring the necessity for perpetual research and development of novel therapeutic alternatives. To supplement the existing literatures on NNRTIs, a comprehensive review has been compiled to synthesize this extensive dataset into a comprehensible format for the medicinal chemistry community. In this review, a thorough investigation and meticulous analysis were conducted on the progressions achieved in NNRTIs within the past 8 years (2016-2023), and the experiences and insights gained in the development of inhibitors with varying chemical structures were also summarized. The provision of a crucial point of reference for the development of wide-ranging anti-HIV medications is anticipated.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071603","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
Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety. 揭示肠道微生物群的作用:双向调节药物运输,提高安全性。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-24 DOI: 10.1002/med.22077
Jinyi Wang, Tingting Zhou
{"title":"Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety.","authors":"Jinyi Wang, Tingting Zhou","doi":"10.1002/med.22077","DOIUrl":"https://doi.org/10.1002/med.22077","url":null,"abstract":"<p><p>Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046037","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
Indirect influence on the BDNF/TrkB receptor signaling pathway via GPCRs, an emerging strategy in the treatment of neurodegenerative disorders. 通过 GPCRs 间接影响 BDNF/TrkB 受体信号通路,这是治疗神经退行性疾病的一种新兴策略。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-24 DOI: 10.1002/med.22075
Mirjana Antonijevic, Patrick Dallemagne, Christophe Rochais
{"title":"Indirect influence on the BDNF/TrkB receptor signaling pathway via GPCRs, an emerging strategy in the treatment of neurodegenerative disorders.","authors":"Mirjana Antonijevic, Patrick Dallemagne, Christophe Rochais","doi":"10.1002/med.22075","DOIUrl":"https://doi.org/10.1002/med.22075","url":null,"abstract":"<p><p>Neuronal survival depends on neurotrophins and their receptors. There are two types of neurotrophin receptors: a nonenzymatic, trans-membrane protein of the tumor necrosis factor receptor (TNFR) family-p75 receptor and the tyrosine kinase receptors (TrkR) A, B, and C. Activation of the TrkBR by brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5) promotes neuronal survival, differentiation, and synaptic function. It is shown that in the pathogenesis of several neurodegenerative conditions (Alzheimer's disease, Parkinson's disease, Huntington's disease) the BDNF/TrkBR signaling pathway is impaired. Since it is known that GPCRs and TrkR are regulating several cell functions by interacting with each other and generating a cross-communication in this review we have focused on the interaction between different GPCRs and their ligands on BDNF/TrkBR signaling pathway.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046035","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 recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer. 聚(ADP-核糖)聚合酶抑制剂治疗癌症的最新进展和前景。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-24 DOI: 10.1002/med.22069
Yi-Ru Bai, Wei-Guang Yang, Rui Jia, Ju-Shan Sun, Dan-Dan Shen, Hong-Min Liu, Shuo Yuan
{"title":"The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.","authors":"Yi-Ru Bai, Wei-Guang Yang, Rui Jia, Ju-Shan Sun, Dan-Dan Shen, Hong-Min Liu, Shuo Yuan","doi":"10.1002/med.22069","DOIUrl":"https://doi.org/10.1002/med.22069","url":null,"abstract":"<p><p>Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046036","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
Fenamates: Forgotten treasure for cancer treatment and prevention: Mechanisms of action, structural modification, and bright future. 非那明酸盐:被遗忘的癌症治疗和预防宝藏:作用机制、结构改造和光明前景。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-22 DOI: 10.1002/med.22079
Junfang Li, Xiaodong Wang, Honghua Zhang, Xiaoling Hu, Xue Peng, Weifan Jiang, Linsheng Zhuo, Yan Peng, Guo Zeng, Zhen Wang
{"title":"Fenamates: Forgotten treasure for cancer treatment and prevention: Mechanisms of action, structural modification, and bright future.","authors":"Junfang Li, Xiaodong Wang, Honghua Zhang, Xiaoling Hu, Xue Peng, Weifan Jiang, Linsheng Zhuo, Yan Peng, Guo Zeng, Zhen Wang","doi":"10.1002/med.22079","DOIUrl":"https://doi.org/10.1002/med.22079","url":null,"abstract":"<p><p>Fenamates as classical nonsteroidal anti-inflammatory agents are widely used for relieving pain. Preclinical studies and epidemiological data highlight their chemo-preventive and chemotherapeutic potential for cancer. However, comprehensive reviews of fenamates in cancer are limited. To accelerate the repurposing of fenamates, this review summarizes the results of fenamates alone or in combination with existing chemotherapeutic agents. This paper also explores targets of fenamates in cancer therapy, including COX, AKR family, AR, gap junction, FTO, TEAD, DHODH, TAS2R14, ion channels, and DNA. Besides, this paper discusses other mechanisms, such as regulating Wnt/β-catenin, TGF-β, p38 MAPK, and NF-κB pathway, and the regulation of the expressions of Sp, EGR-1, NAG-1, ATF-3, ErbB2, AR, as well as the modulation of the tumor immune microenvironment. Furthermore, this paper outlined the structural modifications of fenamates, highlighting their potential as promising leads for anticancer drugs.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015807","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
Canonical effects of cytokines on glomerulonephritis: A new outlook in nephrology. 细胞因子对肾小球肾炎的典型影响:肾脏病学的新前景
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-20 DOI: 10.1002/med.22074
Sepideh Zununi Vahed, Seyed Mahdi Hosseiniyan Khatibi, Mohammadreza Ardalan
{"title":"Canonical effects of cytokines on glomerulonephritis: A new outlook in nephrology.","authors":"Sepideh Zununi Vahed, Seyed Mahdi Hosseiniyan Khatibi, Mohammadreza Ardalan","doi":"10.1002/med.22074","DOIUrl":"https://doi.org/10.1002/med.22074","url":null,"abstract":"<p><p>Glomerulonephritis (GN) is an important cause of renal inflammation resulting from kidney-targeted adaptive and innate immune responses and consequent glomerular damage. Given the lack of autoantibodies, immune complexes, or the infiltrating immune cells in some forms of GN, for example, focal segmental glomerulosclerosis and minimal change disease, along with paraneoplastic syndrome and a special form of renal involvement in some viral infections, the likeliest causative scenario would be secreted factors, mainly cytokine(s). Since cytokines can modulate the inflammatory mechanisms, severity, and clinical outcomes of GN, it is rational to consider the umbrella term of cytokine GN as a new outlook to reclassify a group of previously known GN. We focus here, particularly, on cytokines that have the central \"canonical effect\" in the development of GN.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007926","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 tumor microenvironment with photodynamic nanomedicine. 用光动力纳米药物靶向肿瘤微环境。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-16 DOI: 10.1002/med.22072
Suraj Kumar Modi, Pragyan Mohapatra, Priya Bhatt, Aishleen Singh, Avanish Singh Parmar, Aniruddha Roy, Vibhuti Joshi, Manu Smriti Singh
{"title":"Targeting tumor microenvironment with photodynamic nanomedicine.","authors":"Suraj Kumar Modi, Pragyan Mohapatra, Priya Bhatt, Aishleen Singh, Avanish Singh Parmar, Aniruddha Roy, Vibhuti Joshi, Manu Smriti Singh","doi":"10.1002/med.22072","DOIUrl":"https://doi.org/10.1002/med.22072","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is approved for the treatment of certain cancers and precancer lesions. While early Photosensitizers (PS) have found their way to the clinic, research in the last two decades has led to the development of third-generation PS, including photodynamic nanomedicine for improved tumor delivery and minimal systemic or phototoxicity. In terms of nanoparticle design for PDT, we are witnessing a shift from passive to active delivery for improved outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises of a complex and dynamic landscape with myriad potential targets for photodynamic nanocarriers that are surface-modified with ligands. Herein, we review ways to improvise PDT by actively targeting nanoparticles (NPs) to intracellular organelles such as mitochondria or lysosomes and so forth, overcoming the limitations caused by PDT-induced hypoxia, disrupting the blood vascular networks in tumor tissues-vascular targeted PDT (VTP) and targeting immune cells for photoimmunotherapy. We propose that a synergistic outlook will help to address challenges such as deep-seated tumors, metastasis, or relapse and would lead to robust PDT response in patients.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994885","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
Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules. 天然和合成的 5-(3'-吲哚基)恶唑:生物活性、化学合成和高级分子。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-16 DOI: 10.1002/med.22078
Jing-Rui Liu, En-Yu Jiang, Otgonpurev Sukhbaatar, Wei-Hua Zhang, Ming-Zhi Zhang, Guang-Fu Yang, Yu-Cheng Gu
{"title":"Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules.","authors":"Jing-Rui Liu, En-Yu Jiang, Otgonpurev Sukhbaatar, Wei-Hua Zhang, Ming-Zhi Zhang, Guang-Fu Yang, Yu-Cheng Gu","doi":"10.1002/med.22078","DOIUrl":"https://doi.org/10.1002/med.22078","url":null,"abstract":"<p><p>5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994884","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
Incretin-based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future. 临床上治疗心脏代谢疾病的胰岛素疗法:过去、现在和未来。
IF 10.9 1区 医学
Medicinal Research Reviews Pub Date : 2024-08-14 DOI: 10.1002/med.22070
James P Psaltis, Jessica A Marathe, Mau T Nguyen, Richard Le, Christina A Bursill, Chinmay S Marathe, Adam J Nelson, Peter J Psaltis
{"title":"Incretin-based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future.","authors":"James P Psaltis, Jessica A Marathe, Mau T Nguyen, Richard Le, Christina A Bursill, Chinmay S Marathe, Adam J Nelson, Peter J Psaltis","doi":"10.1002/med.22070","DOIUrl":"https://doi.org/10.1002/med.22070","url":null,"abstract":"<p><p>Among newer classes of drugs for type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are incretin-based agents that lower both blood sugar levels and promote weight loss. They do so by activating pancreatic GLP-1 receptors (GLP-1R) to promote glucose-dependent insulin release and inhibit glucagon secretion. They also act on receptors in the brain and gastrointestinal tract to suppress appetite, slow gastric emptying, and delay glucose absorption. Phase 3 clinical trials have shown that GLP-1 RAs improve cardiovascular outcomes in the setting of T2DM or overweight/obesity in people who have, or are at high risk of having atherosclerotic cardiovascular disease. This is largely driven by reductions in ischemic events, although emerging evidence also supports benefits in other cardiovascular conditions, such as heart failure with preserved ejection fraction. The success of GLP-1 RAs has also seen the evolution of other incretin therapies. Tirzepatide has emerged as a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, with more striking effects on glycemic control and weight reduction than those achieved by isolated GLP-1R agonism alone. This consists of lowering glycated hemoglobin levels by more than 2% and weight loss exceeding 15% from baseline. Here, we review the pharmacological properties of GLP-1 RAs and tirzepatide and discuss their clinical effectiveness for T2DM and overweight/obesity, including their ability to reduce adverse cardiovascular outcomes. We also delve into the mechanistic basis for these cardioprotective effects and consider the next steps in implementing existing and future incretin-based therapies for the broader management of cardiometabolic disease.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974647","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
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