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International Union of Basic and Clinical Pharmacology. CXVI: NC-IUPHAR and Pharmacological Reviews: 30+ Years of Collaboration-Editorial. 国际基础与临床药理学联合会。CXVI:NC-IUPHAR 和药理学评论:30 多年的合作--编辑部。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.124.001409
Eliot H Ohlstein
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引用次数: 0
Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases. 硫化氢及其供体在心脏代谢疾病中的药理作用。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.123.000928
Hai-Jian Sun, Qing-Bo Lu, Xue-Xue Zhu, Zhang-Rong Ni, Jia-Bao Su, Xiao Fu, Guo Chen, Guan-Li Zheng, Xiao-Wei Nie, Jin-Song Bian

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs. This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies, including multiomics, intestinal microflora analysis, organoid, and single-cell sequencing techniques, are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assess the current literature to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. SIGNIFICANCE STATEMENT: This comprehensive review covers recent developments in H2S biology and pharmacology in cardiometabolic diseases CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.

心脏代谢疾病(CMDs)是导致全球死亡的主要因素,因此亟需新型治疗干预措施。硫化氢(H2S)作为一种重要的气体递质,在哺乳动物的心脏代谢系统中具有各种生理、病理生理学和药理学影响,因而备受关注。除了在减轻氧化应激和炎症反应方面的作用外,蓬勃发展的研究还强调了 H2S 通过过硫化作用调节蛋白质的重要性,这是一种众所周知的与慢性阻塞性肺疾病发病机制密切相关的修饰。值得注意的是,包括多组学、肠道微生物菌群分析、类器官和单细胞测序技术在内的先进方法因其能够为生物医学研究提供全面的见解而日益受到重视。这些新兴方法有望描述 H2S 在健康和疾病中的药理作用。我们将批判性地评估当前的文献,以阐明 H2S 在疾病中的作用,同时还将划定它们为基于 H2S 的 CMD 药物疗法带来的机遇和挑战。意义声明 这篇综合综述涵盖了 CMDs 中 H2S 生物学和药理学的最新进展。内源性 H2S 及其供体通过调节多种蛋白质和信号通路,为 CMDs 的治疗带来了巨大希望。新技术的出现将大大推动 H2S 的药理学研究和临床转化。
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引用次数: 0
Conotoxins Targeting Voltage-Gated Sodium Ion Channels. 针对电压门控钠离子通道的芋螺毒素。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.123.000923
Shengrong Pei, Nan Wang, Zaoli Mei, Dongting Zhangsun, David J Craik, J Michael McIntosh, Xiaopeng Zhu, Sulan Luo

Voltage-gated sodium (NaV) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases, such as epilepsy, neuropathic pain, psychosis, autism, and cardiac arrhythmia. Many venom peptides selectively act on NaV channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense but which are also valuable pharmacological tools for the identification and/or treatment of human diseases. Typically, conotoxins contain two or three disulfide bonds, and these internal crossbraces contribute to conotoxins having compact, well defined structures and high stability. Of the conotoxins containing three disulfide bonds, some selectively target mammalian NaV channels and can block, stimulate, or modulate these channels. Such conotoxins have great potential to serve as pharmacological tools for studying the functions and characteristics of NaV channels or as drug leads for neurologic diseases related to NaV channels. Accordingly, discovering or designing conotoxins targeting NaV channels with high potency and selectivity is important. The amino acid sequences, disulfide bond connectivity, and three-dimensional structures are key factors that affect the biological activity of conotoxins, and targeted synthetic modifications of conotoxins can greatly improve their activity and selectivity. This review examines NaV channel-targeted conotoxins, focusing on their structures, activities, and designed modifications, with a view toward expanding their applications. SIGNIFICANCE STATEMENT: NaV channels are crucial in various neurologic diseases. Some conotoxins selectively target NaV channels, causing either blockade or activation, thus enabling their use as pharmacological tools for studying the channels' characteristics and functions. Conotoxins also have promising potential to be developed as drug leads. The disulfide bonds in these peptides are important for stabilizing their structures, thus leading to enhanced specificity and potency. Together, conotoxins targeting NaV channels have both immediate research value and promising future application prospects.

电压门控钠(NaV)通道与动作电位的产生和传递密切相关,这些通道的功能障碍可能导致神经系统疾病,如癫痫、神经性疼痛、精神病、自闭症和心律失常。许多毒液肽会选择性地作用于 NaV 通道。其中包括芋螺毒素,芋螺毒素是锥螺为捕捉猎物或自卫而分泌的神经毒素,同时也是识别和/或治疗人类疾病的重要药理学工具。芋螺毒素通常含有两个或三个二硫键,这些内部交叉架使芋螺毒素具有紧凑、明确的结构和高稳定性。在含有三个二硫键的芋螺毒素中,有些可选择性地靶向哺乳动物的 NaV 通道,并能阻断、刺激或调节这些通道。这类芋螺毒素具有巨大的潜力,可作为研究 NaV 通道功能和特性的药理学工具,或作为治疗与 NaV 通道有关的神经系统疾病的药物线索。因此,发现或设计具有高效力和高选择性的针对 NaV 通道的芋螺毒素非常重要。氨基酸序列、二硫键连接和三维结构是影响芋螺毒素生物活性的关键因素,对芋螺毒素进行有针对性的合成修饰可大大提高其活性和选择性。本综述探讨了以 NaV 通道为靶标的芋螺毒素,重点关注其结构、活性和设计修饰,以期扩大其应用范围。意义声明 NaV 通道在各种神经系统疾病中至关重要。一些芋螺毒素可选择性地靶向 NaV 通道,导致阻断或激活,因此可用作研究通道特性和功能的药理学工具。芋螺毒素还具有开发药物先导的潜力。这些肽中的二硫键对稳定其结构非常重要,从而提高了特异性和药效。总之,靶向 NaV 通道的芋螺毒素既有直接的研究价值,又有广阔的应用前景。
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引用次数: 0
Intestinal Barrier, Immunity and Microbiome: Partners in the Depression Crime. 肠道屏障、免疫力和微生物组:抑郁症犯罪中的合作伙伴。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.124.001202
Eva M Medina-Rodríguez, José Martínez-Raga, Yolanda Sanz

Depression is a highly prevalent disorder and a leading cause of disability worldwide. It has a major impact on the affected individual and on society as a whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, the gut microbiome has emerged as a promising alternative target for treating and preventing depressive disorders. However, the microbes that form this ecosystem do not act alone but are part of a complicated network connecting the gut and the brain that influences our mood. Host cells that are in intimate contact with gut microbes, such as the epithelial cells forming the gut barrier and the immune cells in their vicinity, play a key role in the process. These cells continuously shape immune responses to maintain healthy communication between gut microbes and the host. In this article, we review how the interplay among epithelial cells, the immune system, and gut microbes mediates gut-brain communication to influence mood. We also discuss how advances in our knowledge of the mechanisms underlying the gut-brain axis could contribute to addressing depression. SIGNIFICANCE STATEMENT: This review does not aim to systematically describe intestinal microbes that might be beneficial or detrimental for depression. We have adopted a novel point of view by focusing on potential mechanisms underlying the crosstalk between gut microbes and their intestinal environment to control mood. These pathways could be targeted by well defined and individually tailored dietary interventions, microbes, or microbial metabolites to ameliorate depression and decrease its important social and economic impact.

抑郁症是一种高发疾病,也是导致全球残疾的主要原因。它对患者和整个社会都有重大影响。令人遗憾的是,目前对这种疾病的治疗对许多患者来说都是不够的。近年来,肠道微生物组已成为治疗和预防抑郁症的一个很有前景的替代目标。然而,构成这一生态系统的微生物并不是单独行动的,而是连接肠道和大脑的复杂网络的一部分,它影响着我们的情绪。与肠道微生物密切接触的宿主细胞,如构成肠道屏障的上皮细胞及其附近的免疫细胞,在这一过程中发挥着关键作用。这些细胞不断形成免疫反应,以保持肠道微生物与宿主之间的健康交流。在本文中,我们将回顾上皮细胞、免疫系统和肠道微生物之间的相互作用如何介导肠道与大脑之间的交流,从而影响情绪。我们还讨论了我们对肠道-大脑轴机制的认识的进步如何有助于解决抑郁症问题。意义声明 本综述并不旨在系统描述可能对抑郁症有益或有害的肠道微生物。我们采用了一种新的视角,重点关注肠道微生物与其肠道环境之间控制情绪的潜在串扰机制。这些途径可以通过明确定义的、单独定制的饮食干预、微生物或微生物代谢物来改善抑郁症,并减少其对社会和经济的重要影响。
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引用次数: 0
The Development of Cannabinoids as Therapeutic Agents in the United States. 大麻素作为治疗药物在美国的发展。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.123.001121
Conor H Murray, Brenda M Gannon, Peter J Winsauer, Ziva D Cooper, Marcus S Delatte

Cannabis is one of the oldest and widely used substances in the world. Cannabinoids within the cannabis plant, known as phytocannabinoids, mediate cannabis' effects through interactions with the body's endogenous cannabinoid system. This endogenous system, the endocannabinoid system, has important roles in physical and mental health. These roles point to the potential to develop cannabinoids as therapeutic agents while underscoring the risks related to interfering with the endogenous system during nonmedical use. This scoping narrative review synthesizes the current evidence for both the therapeutic and adverse effects of the major (i.e., Δ9-tetrahydrocannabinol and cannabidiol) and lesser studied minor phytocannabinoids, from nonclinical to clinical research. We pay particular attention to the areas where evidence is well established, including analgesic effects after acute exposures and neurocognitive risks after acute and chronic use. In addition, drug development considerations for cannabinoids as therapeutic agents within the United States are reviewed. The proposed clinical study design considerations encourage methodological standards for greater scientific rigor and reproducibility to ultimately extend our knowledge of the risks and benefits of cannabinoids for patients and providers. SIGNIFICANCE STATEMENT: This work provides a review of prior research related to phytocannabinoids, including therapeutic potential and known risks in the context of drug development within the United States. We also provide study design considerations for future cannabinoid drug development.

大麻是世界上历史最悠久、使用最广泛的物质之一。大麻植物中的大麻素(称为植物大麻素)通过与人体的内源性大麻素系统相互作用来介导大麻的作用。这种内源性系统,即内源性大麻素系统,在身心健康方面发挥着重要作用。这些作用显示了将大麻素开发为治疗药物的潜力,同时也强调了在非医疗使用过程中干扰内源性系统的相关风险。本综述综述了从非临床研究到临床研究的主要植物大麻素(即Δ9-四氢大麻酚和大麻二酚)和研究较少的次要植物大麻素的治疗效果和不良反应的现有证据。我们特别关注证据确凿的领域,包括急性接触后的镇痛效果以及急性和慢性使用后的神经认知风险。此外,我们还回顾了在美国将大麻素作为治疗药物的药物开发注意事项。拟议的临床研究设计考虑因素鼓励制定方法标准,以提高科学严谨性和可重复性,最终扩大我们对大麻素对患者和提供者的风险和益处的了解。意义声明 本研究综述了之前与植物大麻素有关的研究,包括治疗潜力和美国药物开发过程中的已知风险。我们还提供了未来大麻素药物开发的研究设计注意事项。
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引用次数: 0
International Union of Basic and Clinical Pharmacology CXIV: Orexin Receptor Function, Nomenclature and Pharmacology. 国际基础和临床药理学联盟第 CXIV 期:俄瑞欣受体的功能、命名和药理学。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.123.000953
Jyrki P Kukkonen, Laura H Jacobson, Daniel Hoyer, Maiju K Rinne, Stephanie L Borgland

The orexin system consists of the peptide transmitters orexin-A and -B and the G protein-coupled orexin receptors OX1 and OX2 Orexin receptors are capable of coupling to all four families of heterotrimeric G proteins, and there are also other complex features of the orexin receptor signaling. The system was discovered 25 years ago and was immediately identified as a central regulator of sleep and wakefulness; this is exemplified by the symptomatology of the disorder narcolepsy with cataplexy, in which orexinergic neurons degenerate. Subsequent translation of these findings into drug discovery and development has resulted to date in three clinically used orexin receptor antagonists to treat insomnia. In addition to sleep and wakefulness, the orexin system appears to be a central player at least in addiction and reward, and has a role in depression, anxiety and pain gating. Additional antagonists and agonists are in development to treat, for instance, insomnia, narcolepsy with or without cataplexy and other disorders with excessive daytime sleepiness, depression with insomnia, anxiety, schizophrenia, as well as eating and substance use disorders. The orexin system has thus proved an important regulator of numerous neural functions and a valuable drug target. Orexin prepro-peptide and orexin receptors are also expressed outside the central nervous system, but their potential physiological roles there remain unknown. SIGNIFICANCE STATEMENT: The orexin system was discovered 25 years ago and immediately emerged as an essential sleep-wakefulness regulator. This discovery has tremendously increased the understanding of these processes and has thus far resulted in the market approval of three orexin receptor antagonists, which promote more physiological aspects of sleep than previous hypnotics. Further, orexin receptor agonists and antagonists with different pharmacodynamic properties are in development since research has revealed additional potential therapeutic indications. Orexin receptor signaling is complex and may represent novel features.

奥曲肽系统由多肽递质奥曲肽-A 和-B 以及与 G 蛋白偶联的奥曲肽受体 OX1 和 OX2 组成。奥曲肽受体能够与所有四种异三聚体 G 蛋白家族偶联,奥曲肽受体的信号传导还具有其他复杂的特征。该系统于 25 年前被发现,并立即被确定为睡眠和觉醒的中枢调节器;嗜睡症伴惊厥的症状就是一个例证,在这种疾病中,奥曲肽能神经元会退化。这些发现随后被转化为药物的发现和开发,迄今已有三种治疗失眠的奥曲肽受体拮抗剂在临床上使用。除了睡眠和觉醒之外,奥曲肽系统似乎至少在成瘾和奖赏方面发挥着核心作用,并在抑郁、焦虑和疼痛门控方面发挥作用。目前正在开发更多的拮抗剂和激动剂,用于治疗失眠、伴有或不伴有惊厥的嗜睡症和其他白天过度嗜睡的疾病、伴有失眠的抑郁症、焦虑症、精神分裂症以及饮食和药物使用障碍等。因此,奥曲肽系统已被证明是众多神经功能的重要调节器和有价值的药物靶点。奥曲肽前体和奥曲肽受体在中枢神经系统之外也有表达,但它们在中枢神经系统中的潜在生理作用尚不清楚。意义声明 25 年前,人们发现了奥曲肽系统,并立即将其视为睡眠-觉醒的重要调节器。这一发现极大地提高了人们对这些过程的认识,迄今已有三种奥曲肽受体拮抗剂获得市场批准,它们比以往的催眠药更能促进生理性睡眠。此外,具有不同药效学特性的奥曲肽受体激动剂和拮抗剂也在开发中,因为研究发现了更多潜在的治疗适应症。奥曲肽受体信号传导非常复杂,可能具有新的特征。
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引用次数: 0
The Enduring Impact of Pharmacological Reviews-Editorial. 药理学评论的持久影响--社论。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.124.000991
David R Sibley
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引用次数: 0
Cardiovascular Pharmacogenetics: From Discovery of Genetic Association to Clinical Adoption of Derived Test. 心血管药物遗传学:从发现遗传关联到临床采用衍生测试。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.123.000750
Benoît Delabays, Katerina Trajanoska, Joshua Walonoski, Vincent Mooser

Recent breakthroughs in human genetics and in information technologies have markedly expanded our understanding at the molecular level of the response to drugs, i.e., pharmacogenetics (PGx), across therapy areas. This review is restricted to PGx for cardiovascular (CV) drugs. First, we examined the PGx information in the labels approved by regulatory agencies in Europe, Japan, and North America and related recommendations from expert panels. Out of 221 marketed CV drugs, 36 had PGx information in their labels approved by one or more agencies. The level of annotations and recommendations varied markedly between agencies and expert panels. Clopidogrel is the only CV drug with consistent PGx recommendation (i.e., "actionable"). This situation prompted us to dissect the steps from discovery of a PGx association to clinical translation. We found 101 genome-wide association studies that investigated the response to CV drugs or drug classes. These studies reported significant associations for 48 PGx traits mapping to 306 genes. Six of these 306 genes are mentioned in the corresponding PGx labels or recommendations for CV drugs. Genomic analyses also highlighted the wide between-population differences in risk allele frequencies and the individual load of actionable PGx variants. Given the high attrition rate and the long road to clinical translation, additional work is warranted to identify and validate PGx variants for more CV drugs across diverse populations and to demonstrate the utility of PGx testing. To that end, pre-emptive PGx combining genomic profiling with electronic medical records opens unprecedented opportunities to improve healthcare, for CV diseases and beyond. SIGNIFICANCE STATEMENT: Despite spectacular breakthroughs in human molecular genetics and information technologies, consistent evidence supporting PGx testing in the cardiovascular area is limited to a few drugs. Additional work is warranted to discover and validate new PGx markers and demonstrate their utility. Pre-emptive PGx combining genomic profiling with electronic medical records opens unprecedented opportunities to improve healthcare, for CV diseases and beyond.

人类遗传学和信息技术的最新突破极大地拓展了我们在分子水平上对药物反应的理解,即药物遗传学(PGx),涉及多个治疗领域。本综述仅限于心血管(CV)药物的 PGx。首先,我们研究了欧洲、日本和北美监管机构批准的标签中的 PGx 信息以及专家小组的相关建议。在 221 种上市的 CV 药物中,有 36 种药物的标签中的 PGx 信息获得了一个或多个机构的批准。不同机构和专家小组的注释和建议水平存在明显差异。氯吡格雷是唯一一种具有一致的 PGx 建议(即 "可采取行动")的 CV 药物。这种情况促使我们剖析从发现 PGx 关联到临床转化的各个步骤。我们发现有 101 项全基因组关联研究调查了对冠心病药物或药物类别的反应。这些研究报告了映射到 306 个基因上的 48 个 PGx 性状的重要关联。在这 306 个基因中,有 6 个基因在相应的 PGx 标签或 CV 药物建议中被提及。基因组分析还突显了人群间风险等位基因频率的巨大差异,以及可采取行动的 PGx 变异的个体负荷。考虑到高损耗率和临床转化的漫长道路,有必要开展更多的工作,在不同人群中识别和验证更多 CV 药物的 PGx 变异,并证明 PGx 检测的效用。为此,将基因组分析与电子病历相结合的预防性 PGx 为改善冠心病及其他疾病的医疗保健带来了前所未有的机遇。意义声明 尽管人类分子遗传学和信息技术取得了惊人的突破,但支持心血管领域药物遗传学(PGx)检测的一致证据仅限于少数几种药物。我们需要做更多的工作来发现和验证新的药物基因标记物,并证明它们的效用。将基因组分析与电子病历相结合的先期药物基因学检测为改善心血管疾病及其他疾病的医疗保健提供了前所未有的机遇。
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引用次数: 0
The Art of Finding the Right Drug Target: Emerging Methods and Strategies. 寻找正确药物靶点的艺术:新兴方法和策略。
IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-15 DOI: 10.1124/pharmrev.123.001028
Zi-Chang Jia, Xue Yang, Yi-Kun Wu, Min Li, Debatosh Das, Mo-Xian Chen, Jian Wu

Drug targets are specific molecules in biological tissues and body fluids that interact with drugs. Drug target discovery is a key component of drug discovery and is essential for the development of new drugs in areas such as cancer therapy and precision medicine. Traditional in vitro or in vivo target discovery methods are time-consuming and labor-intensive, limiting the pace of drug discovery. With the development of modern discovery methods, the discovery and application of various emerging technologies have greatly improved the efficiency of drug discovery, shortened the cycle time, and reduced the cost. This review provides a comprehensive overview of various emerging drug target discovery strategies, including computer-assisted approaches, drug affinity response target stability, multiomics analysis, gene editing, and nonsense-mediated mRNA degradation, and discusses the effectiveness and limitations of the various approaches, as well as their application in real cases. Through the review of the aforementioned contents, a general overview of the development of novel drug targets and disease treatment strategies will be provided, and a theoretical basis will be provided for those who are engaged in pharmaceutical science research. SIGNIFICANCE STATEMENT: Target-based drug discovery has been the main approach to drug discovery in the pharmaceutical industry for the past three decades. Traditional drug target discovery methods based on in vivo or in vitro validation are time-consuming and costly, greatly limiting the development of new drugs. Therefore, the development and selection of new methods in the drug target discovery process is crucial.

药物靶点是生物组织和体液中与药物相互作用的特定分子。药物靶点发现是药物发现的关键组成部分,对癌症治疗和精准医疗等领域的新药开发至关重要。传统的体外或体内靶点发现方法耗时耗力,限制了药物发现的步伐。随着现代发现方法的发展,各种新兴技术的发现和应用大大提高了药物发现的效率,缩短了周期,降低了成本。本综述全面介绍了各种新兴的药物靶点发现策略,包括计算机辅助方法、药物亲和力反应靶点稳定性、多组学分析、基因编辑和 NMD 等,并讨论了各种方法的有效性和局限性,以及在实际案例中的应用。通过对上述相关内容的综述,将为新型药物靶点的开发和疾病治疗策略提供一个总体概况,并为从事药物科学研究的人员提供理论依据。意义陈述 基于靶点的药物发现是过去三十年制药行业药物发现的主要方法。传统的基于体内或体外验证的药物靶点发现方法耗时长、成本高,极大地限制了新药的开发。因此,在药物靶点发现过程中开发和选择新方法至关重要。
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引用次数: 0
Hope on the Horizon: Promising Therapies for Steatotic Liver Disease 地平线上的希望有望治愈脂肪肝的疗法
IF 21.1 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-07-01 DOI: 10.1124/pharmrev.124.001269
Amirhossein Sahebkar, Ali H. Eid
Steatotic liver disease (SLD) is a highly prevalent chronic liver disease with significant challenges for global health. The pathophysiology of SLD involves an interplay among genetic, endocrine, and metabolic factors. Successful management of SLD entails accurate diagnosis and disease monitoring through noninvasive methods such as advanced imaging techniques and biomarkers. Many emerging pharmacotherapies for SLD are now in the pipeline, which target different pathways like collagen turnover, fibrogenesis, inflammation, and metabolism. The recent approval of resmetirom for noncirrhotic metabolic dysfunction–associated steatohepatitis (MASH) has been a milestone in addressing the unmet medical need for an efficacious SLD treatment. Finally, the potential of personalized medicine approaches and interdisciplinary cooperation in improving patient outcomes and reducing disease burden should be strongly pursued.
脂肪肝(SLD)是一种高发的慢性肝病,对全球健康构成重大挑战。脂肪肝的病理生理学涉及遗传、内分泌和代谢因素之间的相互作用。成功治疗 SLD 需要通过先进的成像技术和生物标志物等非侵入性方法进行准确诊断和疾病监测。目前,许多针对 SLD 的新兴药物疗法正在研发中,它们针对不同的途径,如胶原周转、纤维生成、炎症和新陈代谢。最近,用于治疗非肝硬化代谢功能障碍相关性脂肪性肝炎(MASH)的瑞美替罗(resmetirom)获得批准,这在满足对有效 SLD 治疗的未满足医疗需求方面具有里程碑意义。最后,应大力挖掘个性化医疗方法和跨学科合作在改善患者预后和减轻疾病负担方面的潜力。
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