Handbook of experimental pharmacology最新文献

{"title":"Icosahedral Boron Clusters as Platforms for Biomedical Applications: From Cellular Bioimaging to In Vivo Theranostics.","authors":"Javier Ordóñez-Hernández, Rosario Núñez","doi":"10.1007/164_2026_830","DOIUrl":"https://doi.org/10.1007/164_2026_830","url":null,"abstract":"<p><p>Icosahedral boron clusters have gained increasing attention as biomedical platforms for integrated imaging and therapy. Their outstanding chemical and metabolic stability, high boron density, and structural adaptability enable the design of multifunctional agents that combine diagnosis and treatment within a single molecular or nanoscale construct. This chapter focuses on the biomedical exploitation of boron cluster-based systems for cellular bioimaging and in vivo theranostics, with particular emphasis on boron neutron capture therapy (BNCT). At the in vitro level, boron clusters have been incorporated into fluorescent probes and photoactive conjugates to investigate structure-property-activity relationships, cellular uptake, organelle targeting, and photodamage and illustrate how subcellular localization controls combined BNCT and photodynamic efficacy. In vivo, Gd-carborane systems exemplify MRI-guided BNCT and GdNCT, evolving from LDL-based nanoplatforms to CAIX-targeted small molecules that couple image-based dosimetry with dual neutron capture at the tumour site. Complementary PET/SPECT-radiolabelled boron clusters and nanocarriers enable quantitative tracking of boron biodistribution, patient selection, and irradiation timing. Furthermore, targeted and nanostructured formulations improve tumour selectivity and therapeutic efficacy while reducing off-target toxicity. This chapter highlights how icosahedral boron clusters have evolved into clinically relevant theranostic platforms that integrate imaging, dosimetry, and therapy, supporting the development of more precise and personalized strategies in cancer diagnosis and treatment.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boron Clusters for Potential Glioblastoma Therapy: Emerging Molecular and Nanostructured Strategies.","authors":"Marcos Couto","doi":"10.1007/164_2026_829","DOIUrl":"https://doi.org/10.1007/164_2026_829","url":null,"abstract":"<p><p>Glioblastoma remains among the most aggressive and treatment-refractory brain tumors, prompting the exploration of alternative therapeutic strategies. Boron clusters including carboranes, metallacarboranes, and dodecaborate-based systems have gained attention as chemically versatile motifs that combine high boron density with unique biological functionality. This chapter reviews recent developments, together with selected seminal studies, in the use of boron cluster-based approaches for potential glioblastoma treatment. Strategies spanning nanostructured delivery platforms and molecularly targeted small molecules are discussed, with emphasis on structure-activity relationships, biological mechanisms, and their integration with boron neutron capture therapy.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boron Clusters in Medicine: Emerging Frontiers in Pharmacology.","authors":"Igor B Sivaev","doi":"10.1007/164_2026_831","DOIUrl":"https://doi.org/10.1007/164_2026_831","url":null,"abstract":"<p><p>The first quarter of the twenty-first century has seen a rapid expansion of research into the medical applications of boron cluster-based compounds. Key areas of this research include the use of polyhedral boron hydrides (carboranes, boranes, and metallacarboranes) as pharmacophore groups in the synthesis of compounds with various types of biological activity, the synthesis of boron-rich compounds for boron neutron capture cancer therapy, and the use of boron clusters as carriers of radiohalogen label in radionuclide diagnostics and therapy. This is an attempt to demonstrate the diversity of research being conducted and to briefly touch upon the most interesting results obtained in this area.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAAR Immunopharmacology.","authors":"Anna Magnesa, Andrea Pacini, Grazia Rutigliano","doi":"10.1007/164_2026_819","DOIUrl":"https://doi.org/10.1007/164_2026_819","url":null,"abstract":"<p><p>Trace amine-associated receptors (TAARs) were originally identified as G protein-coupled receptors involved in monoaminergic signaling within the central nervous system. However, accumulating evidence indicates that TAARs, particularly TAAR1 and TAAR2, are also expressed in the immune system, including circulating leukocytes, lymphocytes, macrophages, and microglia. This chapter reviews current evidence regarding TAAR expression, functional pharmacology, and potential translational relevance within the immune system.Expression studies support a predominant TAAR1/TAAR2 pattern across both innate and adaptive immune-cell populations. Functional studies indicate that TAAR signaling can modulate inflammatory responses through chemotaxis, cytokine production, and immunoglobulin secretion. However, these effects are highly context-dependent, preventing a simple classification of TAAR signaling as either pro-inflammatory or anti-inflammatory.The chapter also discusses the emerging role of TAAR signaling in the pathophysiology of diseases, including inflammatory bowel disease, methamphetamine-associated immune dysfunction during HIV infection, multiple sclerosis, Parkinson's disease, fibromyalgia, and hematological malignancies.Despite growing interest in TAAR immunopharmacology, the current evidence remains largely preclinical and methodologically heterogeneous. Major limitations include incomplete protein-level validation, reliance on immortalized cell lines or mixed-cell populations, species-specific pharmacology of available ligands, and limited understanding of physiological trace amine signaling under basal conditions. Further integrative studies will be required to clarify TAAR pathophysiological significance and determine whether TAAR-targeted strategies may have translational relevance in immune-mediated disorders.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology of Kidney Glucose Transport and Mechanisms of Kidney Protection by SGLT2 Inhibitors.","authors":"Volker Vallon","doi":"10.1007/164_2026_828","DOIUrl":"https://doi.org/10.1007/164_2026_828","url":null,"abstract":"<p><p>The Na⁺-coupled glucose transporter SGLT2 is expressed in the early proximal tubule of the kidney, where it reabsorbs most of the filtered glucose. Drugs that inhibit SGLT2 (SGLT2i) can protect the kidneys in patients with and without type 2 diabetes mellitus. In a nutshell, SGLT2i shift the reabsorption of large amounts of glucose from the early proximal tubule to downstream tubular segments that take up glucose via SGLT1. Non-reabsorbed glucose is lost into the urine associated with an osmotic diuresis. Why should this protect the kidney? This review first outlines the physiology of kidney glucose transport. Then it outlines how primary effects of SGLT2i on the early proximal tubule can explain clinical phenotypes that, according to mediation analyses, are predictors of kidney (and heart) protection by SGLT2i, including an increase in hematocrit and lowering of plasma volume, serum urate levels, and albuminuria. Tubule-glomerular communication forms the physiological basis for SGLT2i to acutely lower glomerular filtration rate (GFR) and glomerular capillary pressure. This lowers albuminuria and kidney cortex oxygen demand, which both preserve tubular integrity and GFR in the long run. In the early proximal tubule, SGLT2 is functionally co-regulated with other apical sodium and metabolite transporters. This explains why SGLT2i initially excrete more sodium than expected and are uricosuric, lowering plasma volume and serum urate levels. SGLT2i lower early proximal tubule glucotoxicity and by shifting transport downstream better distribute tubular transport burden and energy needs. Moreover, the transport shift tricks the kidney by simulating \"systemic hypoxia\" at the oxygen sensors in outer medullary interstitial cells. The resulting release of erythropoietin, together with the osmotic diuresis, enhances hematocrit and thereby oxygen delivery to kidneys and other organs. This is complemented by an SGLT2i-induced insulin-sparing and fasting-like metabolic and anti-inflammatory phenotype and by off-target effects including less microbiotic formation of uremic toxins.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Glucose Thresholds: Nutrition, Glycaemic Dynamics and Vascular Dysfunction in Gestational Diabetes Mellitus.","authors":"Paola Valero, Sarah Maria Barneze Costa, Marilza Vieira Cunha Rudge, Katherin Silva, Eline M van der Beek, Luis Sobrevia","doi":"10.1007/164_2026_823","DOIUrl":"https://doi.org/10.1007/164_2026_823","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) is increasingly diagnosed in women strongly driven by the increase in overweight and obesity in women of childbearing age, yet the literature still addresses this condition more often through the lens of diagnostic glucose thresholds and subsequent nutritional management of glycaemia than through broader concepts of glycaemic dynamics, vascular dysfunction and phenotypic heterogeneity. Both GDM and maternal obesity are associated with altered glycaemia, increased glycaemic variability and endothelial dysfunction within the foetoplacental circulation, with potential consequences for nutrient transfer, foetal growth and later cardiometabolic risk. When these conditions coexist, i.e. gestational diabesity, metabolic and vascular disturbances may be amplified. This review critically examines current evidence on dietary patterns, macronutrients, micronutrients and selected bioactive compounds with hypoglycaemic properties in GDM. Attention is given to CGM-derived indices of glycaemic dynamics and to nutritional mechanisms plausibly linked to endothelial function, including oxidative stress, nitric oxide bioavailability, inflammation and insulin sensitivity. Overall, the evidence suggests promise for higher-quality carbohydrates, dietary fibre, increased protein intake, myo-inositol, vitamin D, selected trace elements, omega-3 fatty acids and probiotics; however, the field is constrained by short interventions, heterogeneous populations, limited use of CGM and a heavy reliance on surrogate metabolic endpoints rather than direct vascular assessment. A more mechanistic and phenotype-aware research strategy is therefore needed before specific nutritional approaches can be considered established tools for improving both glycaemic dynamics and vascular function in GDM and gestational diabesity.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAAR1 Potential for Treatment of Stress Disorders.","authors":"Ziqi Gu, De-Nong Liu, Yun-Ai Su","doi":"10.1007/164_2026_822","DOIUrl":"https://doi.org/10.1007/164_2026_822","url":null,"abstract":"<p><p>Substantial evidence indicates that stress serves as a major risk factor for various psychiatric disorders, including major depressive disorder (MDD), anxiety disorders, post-traumatic stress disorder (PTSD), and bipolar disorder. Although multiple therapeutic options exist for these conditions, current treatments often fall short of meeting clinical needs. Since the identification of trace amine-associated receptor 1 (TAAR1), studies across diverse animal models have revealed its involvement in modulating stress responses and its potential role in stress-related psychopathologies. Several selective TAAR1 agonists have shown promising efficacy in alleviating certain stress-induced adverse effects. While the underlying mechanisms remain incompletely understood, emerging evidence suggests they may involve TAAR1 expression in key brain regions regulating stress, as well as its modulatory effects on neurotransmitter systems - such as dopamine, serotonin, and glutamate. This chapter summarizes current research on TAAR1, with a focus on the role of TAAR1 ligands in stress-related disorders. Additionally, we briefly discuss TAAR1-related signaling pathways in stress regulation and the pharmacology of TAAR1 agonists.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Trace Amine-Associated Receptor Signalling.","authors":"Lesha Pretorius, Carine Smith","doi":"10.1007/164_2026_818","DOIUrl":"https://doi.org/10.1007/164_2026_818","url":null,"abstract":"<p><p>Most TAAR-related drug discovery research which has advanced to clinical trials has focused on neuropsychiatric disease. Unfortunately, most studies are either conducted on males only or male and female data are not presented separately to inform on sex specificity of findings. As sex bias is highly prevalent in neuropsychiatric disease, this relative lack of considering sex as a potential confounding factor in these studies hampers complete elucidation of mechanisms at play. Therefore, in this chapter, we focus on the three TAARs for which most research data have been generated (TAAR1, TAAR5 and TAAR8) and summarise sex differences that have been reported in terms of TAAR expression and/or function, with consideration of species differences. In addition, given the sparsity of this information, we expanded our literature search to also include a discussion of role players at different levels of the trace amine signalling pathways - e.g. TAAR ligands. The role of oestrogen as potential TAAR modulator is also discussed. Integrating this information, we provide a critical discussion on whether significant sex differences are likely to exist in TAAR signalling. Finally, we make recommendations on research priorities going forward to ensure that TAAR-focused therapeutics development research is equally beneficial to both males and females.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAAR1 as a Potential Alternate Molecular Target to GLP-1 for Novel Anti-diabetic, Anti-obesity Medications.","authors":"Rhianna K Lenham, Fatema Elgammal, Scott V Harding, Mark D Berry","doi":"10.1007/164_2026_821","DOIUrl":"https://doi.org/10.1007/164_2026_821","url":null,"abstract":"<p><p>Metabolic syndrome affects over 30% of the global population and is characterised by insulin resistance, obesity and dyslipidaemia, all of which significantly increase the development of chronic metabolic disorders including type 2 diabetes mellitus (T2DM). Over time, existing antihyperglycaemic treatments typically become ineffective due to changes in disease progression, highlighting the importance for the continued development of new therapeutic agents which exert their effects through diverse/ novel mechanisms.This chapter reviews the emerging role of trace amine-associated receptor 1 (TAAR1) as a regulator of metabolic function. Whilst research into TAAR1 agonism has predominantly focused within the central nervous system for application in schizophrenia treatments, emerging preclinical and clinical evidence demonstrates that TAAR1 activation enhances glucose-stimulated insulin secretion and regulates dopaminergic pathways in addiction and reward processes. Comparisons with incretin mimetic therapies, including semaglutide - a glucagon-like peptide-1 (GLP-1) receptor agonist - reveal significant mechanistic overlap, alongside potential advantages including a more favourable metabolic safety profile. Collectively these findings position TAAR1 as a promising target with the potential to address both physiological and neurobehavioural aspects of metabolic disease.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Inflammation: How Mast Cells Control Vascular Integrity.","authors":"Julissa González-González, Mónica Díaz-Coránguez, Claudia González-Espinosa","doi":"10.1007/164_2026_813","DOIUrl":"https://doi.org/10.1007/164_2026_813","url":null,"abstract":"<p><p>Blood vessel function is highly modulated by the presence of pro-inflammatory mediators secreted by distinct immune cells. Among them, mast cells (MCs) constitute one of the most important innate immune cell types that can initiate inflammatory reactions and modify vascular permeability. Although it is widely accepted that chemical compound-mediated communication between MCs and endothelial cells occurs and is physiologically relevant, new findings on the role of MCs in the generation of vascular networks in normal and pathological conditions (such as tumor growth) suggest a closer relationship between that immune cell and blood vessel function. In this chapter, we discuss some of the most important cellular and molecular characteristics of normal and intratumoral blood vessels, making emphasis on those alterations related to adhesion molecules and regulators of barrier properties of endothelial cells. Then, evidence showing the participation of MCs and its mediators in the generation of intratumoral blood vessels is presented. Finally, we discuss new anti-angiogenic therapies that have been developed based on the new knowledge about the relationship between immune and endothelial cells.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}