Pharmacological Reviews最新文献

{"title":"Reharnessing the therapeutic potential of gallium-based compounds in oncology: From the laboratory to the clinic.","authors":"Christopher R Chitambar, Casey J Zoss, Mona M Al-Gizawiy, Kathleen M Schmainda, Jennifer M Connelly","doi":"10.1016/j.pharmr.2026.100138","DOIUrl":"10.1016/j.pharmr.2026.100138","url":null,"abstract":"<p><p>Despite advances in the treatment of certain malignancies, it is anticipated that there will be 626,140 cancer deaths in the United States in 2026. Thus, there remains a great need to develop new antineoplastic drugs with unique mechanisms of action distinct from those of existing drugs. Also relevant is revisiting agents that showed promise in early research. Some of these agents struggled to advance for reasons including an incomplete understanding of their molecular targets and insufficient commitment to pursuing their development. Gallium compounds initially gained attention as radiogallium ⁶⁷Ga complexes for tumor imaging in cancer patients, but were later found in clinical trials of nonradioactive gallium nitrate to have antineoplastic activity against lymphoma and urothelial malignancies. Coincident with this, tris(8-quinolinolato)gallium(III) has been shown to be active against solid tumors and has now re-emerged in clinical trials as oral AP-002. Subsequent investigations showed that gallium exerts its antineoplastic activity by disrupting iron-dependent processes essential to cancer development and growth. Recent preclinical studies of oral gallium maltolate demonstrated its activity against glioblastoma, an aggressive brain tumor, leading to a Food and Drug Administration-approved phase 1 clinical trial for patients with relapsed glioblastoma. This review will focus on the evolution of gallium compounds in malignancy; advances in our knowledge of their mechanisms of action and tumor resistance; their interactions with cellular iron homeostasis and other targets; the past and present preclinical and clinical experience with gallium compounds; and the development of promising gallium-based agents on the horizon. SIGNIFICANCE STATEMENT: Gallium compounds showed anticancer activity in early clinical studies; however, an incomplete understanding of their mechanisms of action and resistance hindered the selection of patients most likely to benefit from treatment. Herein, we review the development of gallium compounds from early preclinical research to clinical trials for cancer. Recent insights into gallium's molecular targets have advanced the translation of gallium from the laboratory to a clinical trial of oral gallium maltolate in glioblastoma. Newer gallium compounds are being developed; their advancement is eagerly anticipated.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 4","pages":"100138"},"PeriodicalIF":20.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265462","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":"Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.","authors":"Afshin Derakhshani, Leela Mahajan, Kyle Lesack, Navid Saranjam, Khashayarsha Khazaie, Gunnar Pejler, Roman Krawetz, Laura E Edgington-Mitchell, Henry R Maun, Antoine Dufour","doi":"10.1016/j.pharmr.2026.100144","DOIUrl":"10.1016/j.pharmr.2026.100144","url":null,"abstract":"<p><p>Mast cells (MCs) are versatile, multifunctional immune cells with broad roles in physiological homeostasis and pathogenic processes. MCs are found in most tissues, including skin, lungs, intestines, and peritoneum, and they vary in numbers, types, and biological functions. MCs are implicated in host defense against various pathogens, including bacteria, viruses, and fungi. Additionally, MCs are crucial in protecting against toxins, including those present in venoms from multiple species, such as honeybees, snakes, scorpions, and lizards. Although MCs play an essential role in host defense, they are mostly known for their detrimental actions in allergic reactions, such as asthma, food allergy, anaphylaxis, mastocytosis, and various inflammatory skin conditions. Under such conditions, MCs are activated (via IgE-mediated or other mechanisms) and release a range of potent proinflammatory mediators, including tumor necrosis factor α. In addition to cytokines, they are major producers of histamine and various proteases, including chymase, tryptase, and carboxypeptidase A3. As a result, these mediators contribute to the pathological manifestations associated with inflammatory conditions and other disorders. This review focuses mainly on the biological role of MCs and their proteases, with a focus on chymase and tryptase, as well as their inhibitors as candidate therapies for MC-driven diseases. SIGNIFICANCE STATEMENT: Mast cells (MCs) and their proteases are central regulators of tissue homeostasis, barrier defense, and inflammation across multiple organs, but are also associated with numerous diseases. Ongoing research has shown that the function of MCs is highly dependent on their tissue location, where the local tissue environment shapes their phenotype, protease expression, and, consequently, their biological functions. However, further investigation is required to more precisely understand the physiological conditions governing the transition of MCs from maintaining tissue homeostasis to acquiring pathogenic functions, particularly with respect to their protease-dependent activities. By profiling MC heterogeneity using multiomics approaches to map protease-driven signaling networks, it will be possible to gain deeper insight into their functional roles and establish a conceptual framework to guide the development of next-generation, mechanism-based therapeutics that selectively modulate MC activity in human diseases.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 4","pages":"100144"},"PeriodicalIF":20.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339497","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":"Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.","authors":"Conor McQuaid, Michael Sewell, Axel Montagne","doi":"10.1016/j.pharmr.2026.100143","DOIUrl":"10.1016/j.pharmr.2026.100143","url":null,"abstract":"<p><p>Dysfunction of glial and vascular cells is increasingly recognized as a central feature of neurodegenerative diseases. Growing evidence points to disruptions in glial-vascular interactions, which are critical for maintaining the functions of the neurogliovascular unit throughout the lifespan, as key contributors to disease initiation and progression. However, the mechanisms governing this complex intercellular crosstalk and its potential role in disease pathogenesis remain incompletely understood. In this review, we summarize the current understanding of glial-vascular communication across health and disease, with a particular focus on Alzheimer disease, stroke, cerebral small vessel disease, Parkinson disease, Huntington disease, and multiple sclerosis. We highlight emerging cellular and molecular interactions of interest, outline major gaps in our understanding, and discuss innovative tools, including transcriptomics, which are reshaping the study of neurogliovascular dynamics. A central unresolved question is whether glial and/or vascular dysfunction represents the primary initiating event across neurodegenerative diseases, or whether these processes emerge in parallel through shared upstream drivers. Unraveling these interactions may ultimately reveal novel therapeutic opportunities for a broad range of neurodegenerative conditions. SIGNIFICANCE STATEMENT: Neurogliovascular unit interactions are fundamental to brain homeostasis, yet the molecular basis of this crosstalk and its disruption in neurodegeneration remains poorly understood. This review provides the first comprehensive synthesis of molecular mechanisms governing the Neurogliovascular unit interface across physiological and pathological conditions, integrating evidence from related disorders. By consolidating key signaling pathways, disease-associated alterations, and emerging experimental approaches, this review offers a unifying framework to guide biomarker development and therapeutic targeting.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 4","pages":"100143"},"PeriodicalIF":20.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150842","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":"Chronic pain in Alzheimer disease and the role of neuroimmune interactions.","authors":"Marzia Malcangio, George Sideris-Lampretsas","doi":"10.1016/j.pharmr.2026.100149","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100149","url":null,"abstract":"<p><p>Chronic pain conditions affect a large proportion of the global population and pain has tremendous personal and economic impact, affecting quality of life and ability to work while imposing a significant burden on families and health care systems. Neurological disorders and painful conditions are frequently accompanied by chronic pain, which is often jointly diagnosed with age-related neurodegenerative diseases, however, many patients do not receive adequate treatment. This review aims to create a working framework around the issue of under-recognized/undertreated chronic pain in Alzheimer disease by offering an in-depth overview of the mechanisms driving chronic pain and how we can leverage this knowledge to advance therapeutics approaches for these patients with an emphasis on the immune system. SIGNIFICANCE STATEMENT: Chronic pain conditions are prevalent among the aging population, and they positively associate with dementia. The incidence of chronic pain is associated with neuropsychiatric symptoms of dementia and pain management should aim for effective treatments regardless of cognitive status.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 5","pages":"100149"},"PeriodicalIF":20.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584897","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":"Peptide hormone-based combinational pharmacotherapies for chronic metabolic diseases.","authors":"Zara Siu Wa Chui, Yaqian Xue, Xiaoping Wu, Aimin Xu","doi":"10.1016/j.pharmr.2026.100150","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100150","url":null,"abstract":"<p><p>Peptide hormones play a central role in maintaining metabolic homeostasis by integrating complex signaling pathways to coordinate interorgan crosstalk. Aberrant production and/or dysfunction of peptide hormones are important contributors to the pathophysiology of a cluster of interrelated chronic metabolic diseases (CMDs), including obesity, type 2 diabetes mellitus, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, and cardiovascular diseases. These CMDs often co-occur, ranking among the top causes of death and disability in the rapidly aging population. Peptide hormone-based pharmacotherapies are the mainstay of treatment for these CMDs. Analogs and agonists of peptide hormones produced by classical endocrine cells, especially insulin and glucagon-like peptide-1, are cornerstones in managing diabetes and obesity. Furthermore, peptide hormones released from nonclassical endocrine organs, such as liver-secreted fibroblast growth factors 21 and growth differentiation factor 15, have emerged as highly promising therapeutic candidates for obesity-related metabolic comorbidities. These peptide hormones act synergistically and/or complementarily to exert pleiotropic metabolic benefits through their distinct receptors in different target organs/tissues. Combination pharmacotherapies with these peptide hormones are much more effective than monotherapy and hold promise to address the multimorbidity issue in patients with CMDs. This review summarizes recent advances in the pharmacoengineering and pharmacology of these peptide hormone-based long-acting analogs and coagonists and discusses their synergistic and antagonistic interactions in the treatment of CMDs. Furthermore, we highlight major challenges and future perspectives in the clinical development of multiple peptide hormone-based coagonists as safe and effective pharmacotherapy for the management of metabolic comorbidities. SIGNIFICANCE STATEMENT: This review highlights recent clinical advances in combination peptide hormone therapies for chronic metabolic diseases, emphasizing their superior efficacy over monotherapies in addressing metabolic multimorbidity. Summarizing the latest developments in long-acting analogs and coagonists of peptide hormones provides critical insights into their synergistic mechanisms, clinical potential, and future challenges, offering a comprehensive perspective for improving the management of complex metabolic disorders.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 5","pages":"100150"},"PeriodicalIF":20.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606197","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":"Exploration of multifunctional characteristics and regulatory mechanism of promoter G-quadruplexes.","authors":"Ziyi Zhao, Yangzi Zhang, Jingjing Tian, Yuan Su, Shenghao Lin, Keren Chen, Longjiao Zhu, Wentao Xu","doi":"10.1016/j.pharmr.2026.100151","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100151","url":null,"abstract":"<p><p>G-quadruplexes (G4s), a specialized nucleic acid secondary structure, have been found in recent years to be widely distributed in gene promoter regions. Growing evidence has highlighted the significance of G4 structures of promoter region in regulating various biological processes, including transcription and epigenetic regulation. In this review, we first proposed the 8 main characteristics of G-quadruplexes in the promoter region: widespread distribution, positional specificity, structural diversity, precise regulation, genetic modifiability, dynamic reversibility, signal responsiveness, and synergistic regulation. Common G4 regulators were then categorized as natural products, transcription factors and other binding proteins, small molecule ligands, and nucleic acids, which were fully summarized. Then different types of characterization methods for promoter region G4 and its ligands are summarized. Finally, the directions of promoter region G4 applications, including disease diagnosis, bioimaging, synthetic biology, targeted therapies, and antiviral potentials, which have been the focus of recent studies, are sorted out and presented. SIGNIFICANCE STATEMENT: Promoter G-quadruplexes (G4s) are emerging as dynamic and multifunctional regulatory elements that shape transcription, epigenetic states, and cellular responses to environmental cues. By pioneering the definition of 8 key features and corresponding regulatory mechanisms, this review highlights their significant potential as novel targets for therapeutic intervention and provides a comprehensive framework that advances both fundamental understanding and translational exploration of promoter G4s in disease diagnosis, imaging, synthetic biology, and targeted therapy.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 5","pages":"100151"},"PeriodicalIF":20.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471988","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":"Renal aging and associated diseases: Common mechanisms and therapeutic approaches.","authors":"Jabir Aliyu Muhammad, Nadya Marcelina Julianto, Tania Setiawan, Teresa Fiona Fadjaray, Fernando Elbert, Mudasir Hussain, Lawrence Mario Wirawan, Dongjun Jeong, Hyog Young Kwon","doi":"10.1016/j.pharmr.2026.100148","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100148","url":null,"abstract":"<p><p>The kidneys are highly metabolically active organs that undergo a progressive, intrinsic decline in renal function with aging, a process that can be further exacerbated by chronic exposure to oxidative stress, inflammation, hypertension, and various toxins. Studies have shown that the prevalence of acute kidney injury and chronic kidney disease is significantly higher in the elderly. This suggests that the age-related reduction in baseline renal function, rather than advanced age itself, increases the susceptibility to and severity of these disorders after nephrotoxic insults. We comprehensively discuss the emerging recognition of shared molecular and cellular mechanisms underpinning fibrosis and cellular senescence, 2 hallmark features of functional decline seen in renal aging, acute kidney injury, and chronic kidney disease, as well as proposing the interconnection between these events. Furthermore, we highlight therapeutic strategies aimed at mitigating kidney damage and counteracting the effects of aging. These include lifestyle modifications, small-molecule inhibitors, and senotherapeutic approaches such as senolytics and senomorphics. Overall, this work aims to establish a foundation for understanding the pathogenesis of renal aging and related diseases, while also identifying promising avenues for effective therapeutic intervention. SIGNIFICANCE STATEMENT: Cellular senescence and fibrosis intersect in renal aging, acute kidney injury, and chronic kidney disease, highlighting shared pathways that may be targeted to slow disease progression and providing insights into the underlying mechanisms, current interventions, and future strategies for age-related kidney disorders.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 5","pages":"100148"},"PeriodicalIF":20.3,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536547","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":"Recent advances in methotrexate pharmacology and potential therapeutic uses in age-related cardiometabolic and neurodegenerative diseases.","authors":"Arduino A Mangoni, Julie-Ann Hulin, Sara Tommasi","doi":"10.1016/j.pharmr.2026.100147","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100147","url":null,"abstract":"<p><p>Experimental and clinical evidence continues to accumulate, supporting the critical role of dysregulated inflammation, immunity, and redox signaling in the pathophysiology of various age-related cardiometabolic and neurodegenerative diseases. While ongoing research is investigating novel anti-inflammatory and immunomodulatory therapies for such conditions, available antirheumatic drugs may serve a similar purpose. One such drug, methotrexate, has been successfully used at high doses since the 1940s as an anticancer agent and, more recently, at lower doses in patients with autoimmune diseases. Although the effects of methotrexate have traditionally been attributed to its antiproliferative activity via folic acid modulation, additional targets have been identified, including AMP-activated protein kinase, Janus kinase/signal transducer and activator of transcription, high mobility group box 1 protein, the gut microbiota, and additional pharmacological effects of adenosine, a key mediator of methotrexate. The beneficial effects of modulating these targets on downstream inflammatory and immune pathways, cellular senescence, and vascular, metabolic, and brain homeostasis have been increasingly investigated in experimental models. Furthermore, studies conducted over the past 20 years suggest an association between low-dose methotrexate and a decreased risk of certain age-related cardiometabolic and neurodegenerative diseases, particularly in patients with autoimmune conditions. The results of these studies support the potential protective role of methotrexate against age-associated cardiometabolic and neurodegenerative diseases through multiple mechanisms, unlike targeted immunomodulatory and anti-inflammatory drugs, thereby providing a robust framework for investigating its repurposing in future intervention studies. SIGNIFICANCE STATEMENT: New treatments are essential to address the burden of age-related diseases. The important roles of dysregulated inflammation, immunity, and redox signaling in these conditions have spurred research into developing new therapies or repurposing existing drugs to target these dysfunctions. The disease-modifying antirheumatic drug methotrexate has shown potential protective effects against cellular senescence and certain age-related cardiometabolic and neurodegenerative diseases. This knowledge will encourage further research into the repurposing of methotrexate for the treatment of these diseases.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 5","pages":"100147"},"PeriodicalIF":20.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497775","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":"Targeting of kinases to treat neurodegenerative diseases.","authors":"Tara Shomali, Jean-François Trempe","doi":"10.1016/j.pharmr.2026.100128","DOIUrl":"10.1016/j.pharmr.2026.100128","url":null,"abstract":"<p><p>Neurodegenerative diseases, including Alzheimer, Parkinson, and multiple sclerosis, represent a growing global health crisis with limited therapeutic options that address disease progression. Protein kinases, which are crucial regulators of diverse cellular processes such as endolysosomal trafficking, neuroinflammation, and mitochondrial homeostasis, are frequently dysregulated in these conditions, making them attractive drug targets. This review explores the therapeutic potential of targeting key kinases implicated in neurodegeneration, specifically p38 MAPK, BTK, c-Abl/ABL1, CDK5, GSK3, JNK, LRRK2, and PINK1. We delve into their specific roles in disease pathophysiology, current therapeutic strategies, and the structural insights guiding our understanding of these kinases and the development of more selective inhibitors. Although significant challenges remain, particularly regarding selectivity and drug delivery to the brain, the advancements in our understanding of kinase biology and novel therapeutic modalities offer substantial promise for developing disease-modifying treatments. This review highlights the urgent need for continued research to identify new targets and translate these scientific breakthroughs into effective therapies for patients. SIGNIFICANCE STATEMENT: This review outlines the roles of protein kinases in neurodegenerative diseases and highlights emerging strategies for their therapeutic modulation. By integrating current knowledge of kinase signaling, drug development, and pharmacokinetics, this work provides a timely and practical framework to guide the development of disease-modifying treatments in an area of pressing clinical need.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100128"},"PeriodicalIF":20.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513964","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":"Adhesion G protein-coupled receptors.","authors":"Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea de Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz","doi":"10.1016/j.pharmr.2026.100116","DOIUrl":"10.1016/j.pharmr.2026.100116","url":null,"abstract":"<p><p>Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive assessment of the current understanding of aGPCR biology, including a focus on human and mammalian aGPCRs, their evolutionary origins, methodological approaches, and model systems for their investigation, as well as emerging approaches for their therapeutic targeting. SIGNIFICANCE STATEMENT: Adhesion G protein-coupled receptors are versatile cell-surface proteins that integrate structural, biochemical, and physiological functions, with major roles in health and disease. This review summarizes current knowledge of their molecular features, functions in diverse model systems, and emerging opportunities for therapeutic targeting, providing a comprehensive resource that connects basic biology with translational applications across multiple scientific disciplines.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100116"},"PeriodicalIF":20.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531629","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}