Pharmacology & Therapeutics最新文献_第2页

Recent advances in development and delivery of non-viral nucleic acid therapeutics for brain tumor therapy. 用于脑肿瘤治疗的非病毒核酸疗法的开发和输送的最新进展。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-26 DOI: 10.1016/j.pharmthera.2024.108762

Donat Kögel, Achim Temme, Achim Aigner

引用次数: 0

Optimizing drug therapies in cardiac amyloidosis 优化心脏淀粉样变性的药物疗法。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-23 DOI: 10.1016/j.pharmthera.2024.108758

Mohamed Younis, Ikechukwu Ogbu, Dinesh K. Kalra

{"title":"Optimizing drug therapies in cardiac amyloidosis","authors":"Mohamed Younis, Ikechukwu Ogbu, Dinesh K. Kalra","doi":"10.1016/j.pharmthera.2024.108758","DOIUrl":"10.1016/j.pharmthera.2024.108758","url":null,"abstract":"<div><div>Cardiac amyloidosis (CA) is a form of infiltrative, restrictive cardiomyopathy that presents a diagnostic and therapeutic challenge in clinical practice. Historically, it has led to poor prognosis due to limited treatment options. However, advancements in disease awareness, diagnostic tools, and management approaches have led to the beginning of an era characterized by earlier diagnosis and a broader range of treatments. This article examines the advances in treating the two primary forms of cardiac amyloidosis: transthyretin cardiac amyloidosis (ATTR-CA) and light chain mediated cardiac amyloidosis (AL-CA). It highlights therapies for ATTR-CA that focus on interrupting the process of amyloid fibril formation. These therapies include transthyretin stabilizers, gene silencers, and monoclonal antibodies, which have shown the potential to improve patient outcomes and survival rates significantly. As of this writing, tafamidis is the sole Food and Drug Administration (FDA)--approved drug for ATTR-CA; however, experts anticipate several other drugs will gain approval within 1–2 years. Treatment strategies for AL-CA typically involve chemotherapy to inhibit the clonal cell type responsible for excessive AL amyloid fibril production. The prognosis for both types of amyloidosis primarily depends on how much the heart is affected, with most deaths occurring due to progressive heart failure. Effective care for CA patients requires collaboration among specialists from multiple disciplines, such as heart failure cardiology, electrophysiology, hematology/oncology, nephrology, neurology, pharmacology, and palliative care.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108758"},"PeriodicalIF":12.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714812","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

Pathology of idiopathic pulmonary fibrosis with particular focus on vascular endothelium and epithelial injury and their therapeutic potential 特发性肺纤维化的病理学，特别关注血管内皮和上皮损伤及其治疗潜力。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-23 DOI: 10.1016/j.pharmthera.2024.108757

Wenying Lu , Alan Teoh , Maddison Waters , Greg Haug , Ilma Shakeel , Imtaiyaz Hassan , Affan Mahmood Shahzad , Anna-Karin Larsson Callerfelt , Lucilla Piccari , Sukhwinder Singh Sohal

{"title":"Pathology of idiopathic pulmonary fibrosis with particular focus on vascular endothelium and epithelial injury and their therapeutic potential","authors":"Wenying Lu , Alan Teoh , Maddison Waters , Greg Haug , Ilma Shakeel , Imtaiyaz Hassan , Affan Mahmood Shahzad , Anna-Karin Larsson Callerfelt , Lucilla Piccari , Sukhwinder Singh Sohal","doi":"10.1016/j.pharmthera.2024.108757","DOIUrl":"10.1016/j.pharmthera.2024.108757","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) remains a challenging disease with no drugs available to change the trajectory. It is a condition associated with excessive and highly progressive scarring of the lungs with remodelling and extracellular matrix deposition. It is a highly “destructive” disease of the lungs. The diagnosis of IPF is challenging due to continuous evolution of the disease, which also makes early interventions very difficult. The role of vascular endothelial cells has not been explored in IPF in great detail. We do not know much about their contribution to arterial or vascular remodelling, extracellular matrix changes and contribution to pulmonary hypertension and lung fibrosis in general. Endothelial to mesenchymal transition appears to be central to such changes in IPF. Similarly, for epithelial changes, the process of epithelial to mesenchymal transition seem to be the key both for airway epithelial cells and type-2 pneumocytes. We focus here on endothelial and epithelial cell changes and its contributions to IPF. In this review we revisit the pathology of IPF, mechanistic signalling pathways, clinical definition, update on diagnosis and new advances made in treatment of this disease. We discuss ongoing clinical trials with mode of action. A multidisciplinary collaborative approach is needed to understand this treacherous disease for new therapeutic targets.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108757"},"PeriodicalIF":12.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714815","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

Collateral lethality: A unique type of synthetic lethality in cancers 附带致死率：癌症中一种独特的合成致死率。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-23 DOI: 10.1016/j.pharmthera.2024.108755

Zichen Zhao , Lingling Zhu , Yu Luo , Heng Xu , Yan Zhang

{"title":"Collateral lethality: A unique type of synthetic lethality in cancers","authors":"Zichen Zhao , Lingling Zhu , Yu Luo , Heng Xu , Yan Zhang","doi":"10.1016/j.pharmthera.2024.108755","DOIUrl":"10.1016/j.pharmthera.2024.108755","url":null,"abstract":"<div><div>Genetic interactions play crucial roles in cell-essential functions. Intrinsic genetic defects in tumors typically involve gain-of- and loss-of-function mutations in tumor suppressor genes (TSGs) and oncogenes, respectively, providing potential antitumor vulnerabilities. Moreover, tumor cells with TSG deficiencies exhibit heightened sensitivity to the inhibition of compensatory pathways. Synthetic and collateral lethality are two strategies used for exploiting novel drug targets in multiple types of cancer. Collateral lethality is a unique type of synthetic lethality that occurs when passenger genes are co-deleted in neighboring TSGs. Although synthetic lethality has already been successfully demonstrated in clinical practice, antitumor therapeutics based on collateral lethality are predominantly still in the preclinical phase. Therefore, screening for potential genetic interactions within the cancer genome has emerged as a promising approach for drug development. Here, the two conceptual therapeutic strategies that involve the deletion or inactivation of cancer-specific TSGs are discussed. Moreover, existing approaches for screening and identifying potential gene partners are also discussed. Particularly, this review highlights the current advances of “collateral lethality” in the preclinical phase and addresses the challenges involved in translating them into therapeutic applications. This review provides insights into these strategies as new opportunities for the development of personalized antitumor therapies.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108755"},"PeriodicalIF":12.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708544","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

Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation 有利于消除炎症的脂质介质和创新疗法。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-18 DOI: 10.1016/j.pharmthera.2024.108753

Hong Yong Peh , Jianmin Chen

{"title":"Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation","authors":"Hong Yong Peh , Jianmin Chen","doi":"10.1016/j.pharmthera.2024.108753","DOIUrl":"10.1016/j.pharmthera.2024.108753","url":null,"abstract":"<div><div>This review summarizes findings presented at the 19th World Congress of Basic & Clinical Pharmacology 2023 (Glasgow, Scotland, July 3rd to 7th, 2023) from 8 speakers in the field of resolution of inflammation, resolution pharmacology and resolution biology. It is now accepted that the acute inflammatory response is protective to defend the host against infection or tissue injury. Acute inflammation is self-limited and programmed to be limited in space and time: this is achieved through endogenous resolution processes that ensure return to homeostasis. Resolution is brought about by agonist mediators that include specialized pro-resolving lipid mediators (SPMs) and pro-resolving proteins and peptides such as annexin A1 and angiotensin-(1–7), all acting to initiate anti-inflammatory and pro-resolving processes. If the inflammatory reaction remains unchecked through dysfunctional resolution mechanism, it can become chronic and contribute to a plethora of human diseases, including respiratory, cardiovascular, metabolic, allergic diseases, and arthritis. Herein, we discuss how non-resolving inflammation plays a role in the pathogenesis of these diseases. In addition to SPMs, we highlight the discovery, biosynthesis, biofunctions, and latest research updates on innovative therapeutics (including annexin-A1 peptide-mimetic RTP-026, small molecule FPR2 agonist BM-986235/LAR-1219, biased agonist for FPR1/FPR2 Cmpd17b, lipoxin mimetics AT-01-KG and AT-02-CT, melanocortin receptor agonist AP1189, gold nanoparticles, angiotensin-(1–7), and CD300a) that can promote resolution of inflammation directly or through modulation of SPMs production. Drug development strategies based on the biology of the resolution of inflammation can offer novel therapeutic means and/or add-on therapies for the treatment of chronic diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108753"},"PeriodicalIF":12.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680427","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 pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges 天然产品纳米微粒的药效学和药理学机制：发展与挑战。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-18 DOI: 10.1016/j.pharmthera.2024.108754

Junzhe Zhang , Huanhuan Pang , Huan Tang , Qingchao Tu , Fei Xia , Hao Zhang , Yuqing Meng , Guang Han , Jigang Wang , Chong Qiu

{"title":"The pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges","authors":"Junzhe Zhang , Huanhuan Pang , Huan Tang , Qingchao Tu , Fei Xia , Hao Zhang , Yuqing Meng , Guang Han , Jigang Wang , Chong Qiu","doi":"10.1016/j.pharmthera.2024.108754","DOIUrl":"10.1016/j.pharmthera.2024.108754","url":null,"abstract":"<div><div>Natural products such as Traditional Chinese Medicines (TCMs) show great advantages in the treatment and prevention of diseases, but the unclear effective ingredients and mechanisms are key obstacles to restrict their rapid development. Under the guidance of the theoretical guidance of reductionism and the theoretical of allopathic medicine, some researches have indeed achieved some breakthrough results. However, these incomplete methods mainly limited to direct actions or indirect actions (such as the intermediated substances mediated cross-organ or cross-system regulation) mechanism of single active ingredient derived from natural products, which are often inconsistent with Systemism and Harmonizing Medicine and make it difficult to reasonably explain the pharmacodynamics and pharmacological mechanism of most natural products. Actually, effective pharmaceutical ingredients often do not exist in the form of free monomers, but prefer to assembly nanovesicles (NVs) for a combinational pharmacological effect, mainly including self-assembled nanoparticles (SANs) and exosome-like nanoparticles (ELNs). These developments of NVs-based application are a good supplement to existing pharmacological mechanism research. Hence, this review focuses on the developments and strategies of the pharmacodynamics and pharmacological mechanism of NVs-based TCMs under the combining theory of traditional Chinese and western medicine. On this basis, a novel “multidimensional combination” research approach is proposed firstly, which will provide new strategies and directions for breaking through the bottleneck of pharmacological mechanism research, and promote the clinical application of innovative natural products including TCMs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108754"},"PeriodicalIF":12.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680478","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

Exploring the landscape of post-translational modification in drug discovery 探索药物发现中翻译后修饰的全貌。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-16 DOI: 10.1016/j.pharmthera.2024.108749

Yuhao Cao , Tianyi Yu , Ziang Zhu , Yuanjiao Zhang , Shanliang Sun , Nianguang Li , Chunyan Gu , Ye Yang

{"title":"Exploring the landscape of post-translational modification in drug discovery","authors":"Yuhao Cao , Tianyi Yu , Ziang Zhu , Yuanjiao Zhang , Shanliang Sun , Nianguang Li , Chunyan Gu , Ye Yang","doi":"10.1016/j.pharmthera.2024.108749","DOIUrl":"10.1016/j.pharmthera.2024.108749","url":null,"abstract":"<div><div>Post-translational modifications (PTMs) play a crucial role in regulating protein function, and their dysregulation is frequently associated with various diseases. The emergence of epigenetic drugs targeting factors such as histone deacetylases (HDACs) and histone methyltransferase enhancers of zeste homolog 2 (EZH2) has led to a significant shift towards precision medicine, offering new possibilities to overcome the limitations of traditional therapeutics. In this review, we aim to systematically explore how small molecules modulate PTMs. We discuss the direct targeting of enzymes involved in PTM pathways, the modulation of substrate proteins, and the disruption of protein-enzyme interactions that govern PTM processes. Additionally, we delve into the emerging strategy of employing multifunctional molecules to precisely regulate the modification levels of proteins of interest (POIs). Furthermore, we examine the specific characteristics of these molecules, evaluating their therapeutic benefits and potential drawbacks. The goal of this review is to provide a comprehensive understanding of PTM-targeting strategies and their potential for personalized medicine, offering a forward-looking perspective on the evolution of precision therapeutics.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108749"},"PeriodicalIF":12.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666282","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

New drug discovery and development from natural products: Advances and strategies 从天然产品中发现和开发新药物：进展与战略。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-16 DOI: 10.1016/j.pharmthera.2024.108752

Yixin Wang , Fan Wang , Wenxiu Liu , Yifei Geng , Yahong Shi , Yu Tian , Bin Zhang , Yun Luo , Xiaobo Sun

{"title":"New drug discovery and development from natural products: Advances and strategies","authors":"Yixin Wang , Fan Wang , Wenxiu Liu , Yifei Geng , Yahong Shi , Yu Tian , Bin Zhang , Yun Luo , Xiaobo Sun","doi":"10.1016/j.pharmthera.2024.108752","DOIUrl":"10.1016/j.pharmthera.2024.108752","url":null,"abstract":"<div><div>Natural products (NPs) have a long history as sources for drug discovery, more than half of approved drugs are related to NPs, which also exhibit multifaceted advantages in the clinical treatment of complex diseases. However, bioactivity screening of NPs, target identification, and design optimization require continuously improved strategies, the complexity of drug mechanism of action and the limitations of technological strategies pose numerous challenges to the development of new drugs. This review begins with an overview of bioactivity- and target-based drug development patterns for NPs, advances in NP screening and derivatization, and the advantages and problems of major targets such as genes and proteins. Then, target-based drugs as well as identification and validation methods are further discussed to elucidate their mechanism of action. Subsequently, the current status and development trend of the application of traditional and emerging technologies in drug discovery and development of NPs are systematically described. Finally, the collaborative strategy of multi-technology integration and multi-disciplinary intersection is emphasized for the challenges faced in the identification, optimization, activity evaluation, and clinical application of NPs. It is hoped to provide a systematic overview and inspiration for exploring new drugs from natural resources in the future.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108752"},"PeriodicalIF":12.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666286","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

Neurobiology of cancer: Adrenergic signaling and drug repurposing 癌症神经生物学：肾上腺素能信号转导与药物再利用。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-10 DOI: 10.1016/j.pharmthera.2024.108750

Zi-Kai Dong , Yong-Fei Wang , Wei-Ping Li , Wei-Lin Jin

引用次数: 0

The potential therapeutic strategy in combating neurodegenerative diseases: Focusing on natural products 抗击神经退行性疾病的潜在治疗策略：关注天然产品。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-09 DOI: 10.1016/j.pharmthera.2024.108751

Li Gao , Xi-Na Yang , Yi-Xiao Dong , Yi-Jia Han , Xin-Yue Zhang , Xin-Le Zhou , Ying Liu , Fang Liu , Jian-Song Fang , Jian-Long Ji , Zheng-Run Gao , Xue-Mei Qin

{"title":"The potential therapeutic strategy in combating neurodegenerative diseases: Focusing on natural products","authors":"Li Gao , Xi-Na Yang , Yi-Xiao Dong , Yi-Jia Han , Xin-Yue Zhang , Xin-Le Zhou , Ying Liu , Fang Liu , Jian-Song Fang , Jian-Long Ji , Zheng-Run Gao , Xue-Mei Qin","doi":"10.1016/j.pharmthera.2024.108751","DOIUrl":"10.1016/j.pharmthera.2024.108751","url":null,"abstract":"<div><div>Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and Multiple sclerosis (MS), pose a significant global health challenge due to their intricate pathology and limited therapeutic interventions. Natural products represent invaluable reservoirs for combating these neurodegenerative diseases by targeting key pathological hallmarks such as protein aggregation, synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, inflammation, and neuronal cell death. This review provides an in-depth analysis of the mechanisms and therapeutic targets of natural products for their neuroprotective effects. Furthermore, it elucidates the current progress of clinical trials investigating the potential of natural products in delaying neurodegeneration. The objective of this review is to enhance the comprehension of natural products in the prevention and treatment of neurodegenerative diseases, offering new insights and potential avenues for future pharmaceutical research.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108751"},"PeriodicalIF":12.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611506","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