Pharmacology Research & Perspectives最新文献

{"title":"Behavioral Domain-Specific Effects of Positive Modulation of α5 and α6 GABA_A Receptors in a Rat Double-Hit Stress Model.","authors":"Đorđe Đorović, Jovana Aranđelović, Jana Ivanović, Kristina Jezdić, Bojan Batinić, Dishary Sharmin, Prithu Mondal, James M Cook, Miroslav M Savić","doi":"10.1002/prp2.70245","DOIUrl":"10.1002/prp2.70245","url":null,"abstract":"<p><p>Impulsivity is an understudied area of post-traumatic stress disorder, a debilitating disorder specifically associated with stress. We examined reward-related impulsive behavior, anxiety-like behavior, locomotor activity and social behavior in the absence and presence of protracted pharmacological positive modulation of α5- and α6-GABA_A receptors (GL-II-73 and DK-I-56-1, respectively) in male Sprague-Dawley rats exposed to a combination of maternal deprivation (MD) and single prolonged stress (SPS). While locomotor and anxiety-like behavior were not affected in the SPS and MD+SPS groups, the double-hit group treated with DK-I-56-1 exhibited a higher locomotor distance compared with MD+SPS and a higher percentage of open-arm time in the elevated plus maze compared with the control group. In the variable delay-to-signal task of impulsivity, the total number of successful trials and premature responses (PR) in the first stage of the test day were reduced in all groups exposed to stress compared with the controls. Based on PR rates in the first and second set of trials, motor impulsivity was apparently suppressed in all stressed groups, while delay intolerance was suppressed only in the MD+SPS+GL-II-73 group, respectively. In the three-chamber test, social interaction was completely normal, while social recognition was preserved in the MD+SPS+GL-II-73 group. In the resident-intruder test, social play was reduced only in the SPS group. The evaluation of impulsive behavior in the used complex task was hindered by the lack of motivation of stressed rats, which in the case of omission percentage was ameliorated by positive modulation of α5 and α6 GABA_A receptors.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70245"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Sleep Architecture Profiles of Antidepressants in Mice: Pharmacological Characterization of Paroxetine, Sertraline, Duloxetine, Mirtazapine and Vortioxetine.","authors":"Junya Maruoka, Ryo Egami, Yuto Akita, Kohei Kozuka, Yusuke Kakumoto, Tetsuro Kikuchi, Kazuhiko Kume","doi":"10.1002/prp2.70246","DOIUrl":"10.1002/prp2.70246","url":null,"abstract":"<p><p>Sleep is a biological process essential for various brain functions, and patients with major depressive disorder (MDD) frequently experience sleep disturbances. Since such disturbances are both symptoms and risk factors for depression, evaluating the effects of antidepressants on sleep is important for understanding their clinical effectiveness. In this study, we investigated the effects of five antidepressants-paroxetine and sertraline (selective serotonin reuptake inhibitors), duloxetine (a serotonin-norepinephrine reuptake inhibitor), mirtazapine (a noradrenergic and specific serotonergic antidepressant), and vortioxetine (a serotonin reuptake inhibitor and modulator)-on sleep architecture in male mice using cortical electroencephalogram and electromyogram. Paroxetine and sertraline reduced rapid eye movement (REM) sleep, while duloxetine decreased REM sleep and increased non-REM (NREM) sleep. Mirtazapine reduced Wake and increased NREM sleep significantly, while vortioxetine also increased NREM sleep. Interestingly, among the five antidepressants tested, only paroxetine reduced Wake and increased NREM sleep during the dark period when administered prior to the light period. This is the first study to compare the effects of these five compounds on sleep architecture in mice within a single experimental framework. These findings were consistent with clinical observations, suggesting translational relevance. By reporting and comparing the sleep-related pharmacological profiles of these antidepressants, our findings may help guide the selection of appropriate treatments for patients with MDD, particularly those suffering from sleep disturbances.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70246"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual Screening and Zebrafish Phenotype-Based Evaluation Argues Against Repurposing 4-Phenylbutyrate for STXBP1-Related Disorders.","authors":"Aline Frick, Paige Whyte-Fagundes, Scott C Baraban","doi":"10.1002/prp2.70285","DOIUrl":"10.1002/prp2.70285","url":null,"abstract":"<p><p>Syntaxin-binding protein 1 (STXBP1) mutations lead to severe epilepsy, intellectual disability, developmental delay, and movement disorder. Effective treatments for these conditions do not exist. Recent studies in Munc18-1 (STXBP1) C. elegans models demonstrate that 4-phenylbutyrate (4-PBA) or related pharmacological chaperones stabilize Munc18-1 protein levels and rescue locomotion deficits. These studies suggest a novel treatment strategy for these patients. Here, we used a stxbp1a zebrafish model with a profound movement disorder to screen 4-PBA and alternative structural analogs identified using artificial intelligence (AI)-based screening. Automated locomotion assays conducted on larval stxbp1a mutant zebrafish at 5 days post-fertilization (dpf) confirm and extend the movement disorder endophenotype. Drug treatment (4-PBA or 16 identified candidates) failed to rescue the stxbp1a mutant zebrafish locomotion deficit. Electrophysiology studies in a stxbp1b zebrafish model characterized by spontaneous seizure activity (i.e., epilepsy) failed to detect a reduction in ictal-like events with 4-PBA treatment. Taken together, our results suggest caution in repurposing 4-PBA or related compounds for the treatment of STXBP1 disorders.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70285"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Monoterpene Stylosin Induced Anticancer Effects on Human Colon Carcinoma Cells.","authors":"Sara Seyedshazileh, Amirabbas Abdollahi, Mehrdad Iranshahi, Fatemeh B Rassouli","doi":"10.1002/prp2.70287","DOIUrl":"10.1002/prp2.70287","url":null,"abstract":"<p><p>Colorectal carcinoma (CRC) ranks among the top five most common malignancies globally, characterized by a high incidence and poor prognosis. Hepatocyte growth factor receptor (HGFR), a tyrosine kinase oncoprotein, plays a critical role in tumor progression. This study aimed to investigate the effects of stylosin (STL), a natural monoterpene, on human CRC cells, with focus on its potential interactions with HGFR. For computational analysis, the expression of HGFR was assessed in CRC tissues, pharmacokinetics of STL were predicted, and the interaction between STL and HGFR was determined by molecular docking. For experimental studies, STL was isolated from Ferula ovina roots via thin layer chromatography, and its structure was confirmed by ¹H NMR spectroscopy. LoVo cells were treated with STL at concentrations of 25, 50, and 100 μM for 24, 48, 72, 96, and 120 h. Cell viability was assessed by alamarBlue, while apoptosis was evaluated by annexin V-FITC/PI staining followed by flow cytometry analysis. Results demonstrated significant overexpression of HGFR in CRC tissues relative to normal samples. The pharmacokinetic analysis of STL predicted high bioavailability, favorable distribution, and low toxicity risks. Molecular docking predicted a favorable binding affinity of STL to the active site of HGFR. Treatment with STL led to a dose-dependent decrease in cell viability, with the most pronounced cytotoxic effect observed at 100 μM. This was supported by notable morphological changes and increased apoptosis in treated cells. Collectively, the present findings show anticancer activity of STL in CRC cells, with computational predictions suggesting possible HGFR involvement and favorable pharmacokinetic properties. These results provide initial evidence supporting further investigation and position STL as a potent agent against CRC.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70287"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta Analysis of DHA and EPA Supplementation on Cardiovascular Outcomes and Atrial Fibrillation Risk.","authors":"Sepideh Karkon Shayan, Rosull Saadoon Abbood, Sarah F Al-Taie, Paria Ganji Nataj, Maksudova Malika Khamdamjonovna, Siamak Aminnezhad, Yasaman Ghodsi Boushehri, Jabbarov Jamoliddin Sindorovich, Ali Sinehsepehr, Farshad Zare, Seyed Abbas Pakmehr, Elham Abdollahi, Milad Vahedinezhad","doi":"10.1002/prp2.70265","DOIUrl":"10.1002/prp2.70265","url":null,"abstract":"<p><p>Cardiovascular diseases (CVD) remain to impose a main global burden of morbidity and mortality despite advances in anticipation and treatment. Omega-3 fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been extensively studied for potential cardioprotective effects, yet their impact on cardiovascular outcomes remains debated due to heterogeneity in formulation, dose, and patient subgroups. This meta-analysis evaluated the effects of EPA and DHA supplementation on major adverse cardiovascular events (MACE) and atrial fibrillation (AF), including postoperative AF (POAF), in patients with established CVD. A systematic search of Embase, PubMed/MEDLINE, Scopus, and Web of Science (January 2010-December 2021) identified randomized controlled trials (RCTs) of combined EPA + DHA supplementation in secondary prevention or perioperative settings. Data were synthesized using RevMan v5.3 with a random-effects model, and study quality was assessed via the Cochrane RoB 2 tool. From 3682 records, 25 RCTs (n = 25 578 patients) were included. Pooled analysis showed no significant reduction in MACE (effect estimate 0.042 ± 0.0499, Z = 0.850, 95% CI [-0.055, 0.140], p = 0.396; low heterogeneity) or AF/POAF incidence (trend toward reduction: -0.198 ± 0.1498, Z = -1.319, 95% CI [-0.491, 0.096], p = 0.187; modest heterogeneity). Neutral findings likely reflect moderate-dose combined EPA + DHA use, limited subgroup reporting on metabolic comorbidities (e.g., diabetes, hypertriglyceridemia) or concomitant therapies (e.g., statins), and high background guideline-directed medical therapy reducing residual risk. Although omega-3 fatty acids exert anti-inflammatory, antithrombotic, and lipid-modulating effects, this analysis indicates no broad benefit in reducing MACE or AF risk with combined moderate-dose EPA + DHA in heterogeneous post-event populations. Recent evidence highlights more MACE reductions with high-dose purified EPA monotherapy in high-metabolic-risk subgroups, balanced against dose-dependent AF increases at high doses (> 1.5 g/day). Future large-scale RCTs should prioritize biomarker-verified compliance, metabolic/concomitant therapy stratification, and formulation-specific comparisons to define targeted therapeutic roles. Trial Registration: This study has been registered in PROSPERO, and the registration code is 642795.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70265"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acceptability of Atropine Eyedrops Administered Sublingually for Sialorrhea Treatment Related to Neurological Conditions.","authors":"Hugues Michelon, Clémence Lefèvre-Dognin, Julie Paquereau, Raphaëlle Guidoni, Vincent Boudy, Fabrice Ruiz, Thibault Vallet","doi":"10.1002/prp2.70250","DOIUrl":"10.1002/prp2.70250","url":null,"abstract":"<p><p>Off-label use of anticholinergic agents (atropine eye drops) administered sublingually are a first-line treatment in standard clinical practice in France to treat sialorrhea in patients with neurological conditions. The ability and willingness to using and administering such medication have become key factors to ensure safe and effective therapy. Given that the critical aspects for ophthalmic product development differ from those for oral medicine, the objectives of this study were to investigate patient acceptability of atropine eye drops for treating sialorrhea. A multi-centric, cross-sectional study using the CAST-ClinSearch Acceptability Score Test methodology was conducted in France between February 2021 and April 2023. In total, 31 evaluations were collected. Most patients were males (74.2%) and the mean age was 51.6 ± 20 years. Poor acceptability was reported in real-life settings. A lack of a suitable administration device combined with excessive saliva flow and patient disabilities made it difficult to ensure the required dose intake. Due to the bitter taste of the drug, poor palatability of the product appeared to be a key concern for oral administration. Designing a suitable form of atropine in accordance with the specificities of patients with neurological disabilities is needed to ensure the effective treatment of sialorrhea.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70250"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antipsychotic Aripiprazole Induces Cytotoxicity in Bladder Cancer Cells While Preserving Urothelial and Bladder Function.","authors":"Liam A O'Callaghan, Katie Powell, Russ Chess-Williams, Catherine McDermott","doi":"10.1002/prp2.70260","DOIUrl":"10.1002/prp2.70260","url":null,"abstract":"<p><p>Aripiprazole (ARI), an atypical antipsychotic, has demonstrated anticancer activity in several malignancies and may be a candidate for drug repurposing as an intravesical therapy for bladder cancer, particularly non-muscle-invasive bladder cancer (NMIBC). This study evaluated whether brief, intravesical-like ARI exposure could induce cytotoxic effects in bladder cancer cells while preserving normal bladder structure and function. RT4 and T24 bladder cancer cells, together with non-malignant UROtsa urothelial cells, were exposed to ARI (1-300 μM) for 30 min or 2 h, and viability was assessed at 24, 48 and 72 h. Reactive oxygen species (ROS) generation was measured in RT4 and T24 cells after 2 h pretreatment, while caspase-3 activity and stress-associated protein expression were examined in T24 cells. In parallel, an ex vivo porcine bladder model was used to assess the effects of luminal ARI pretreatment (300 μM, 2 h) on urothelial thickness, ATP and acetylcholine release, detrusor contractility, β-adrenergic relaxation, and nerve-evoked responses. ARI reduced viability in a concentration-dependent manner in RT4, T24 and UROtsa cells, with greater cytotoxicity after 2 h pretreatment. In bladder cancer cells, ROS increased only at higher concentrations, whereas ARI increased caspase-3 activity at lower concentrations and altered multiple stress-related proteins in T24 cells. In porcine bladder, ARI preserved urothelial structure and mediator release, maintained detrusor and neurogenic function, and enhanced the inhibitory influence attributed to urothelium-derived inhibitory factor (UDIF). Collectively, these findings identify ARI as a mechanistically active yet bladder-sparing candidate for intravesical repurposing and support its further evaluation as a potential therapy for bladder cancer.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 3","pages":"e70260"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Novel TRPV1 Agonist ST-6631 Improves Swallowing Function in Rat Models of Stroke-Related Dysphagia and Demonstrates Pharmaceutical Advantage Over Capsaicin, by Exhibiting Minimal Pungent and Irritant Properties.","authors":"Masanori Miyauchi, Hiroyuki Kitano, Mami Kochi, Itaru Natsutani, Yuki Mizukami, Yasuyo Maezawa, Kozo Yoshida, Noboru Iwagaki","doi":"10.1002/prp2.70243","DOIUrl":"10.1002/prp2.70243","url":null,"abstract":"<p><p>Dysphagia, often associated with neurological disorders such as stroke, not only damages patients' quality of life, like the joy of engaging with meals, but also adversely affects mortality among patients by increasing risks of getting aspiration pneumonia. There are currently no approved drug-based treatments, leaving dysphagic symptom management as unmet clinical needs. Nevertheless, transient receptor potential vanilloid 1 (TRPV1) channel has gained clinical interest to enhance the sensitivity of sensory nerves that facilitate swallowing reflexes in the pharynx. Here, a novel TRPV1 agonist and antedrug candidate ST-6631 has been introduced, with its therapeutic efficacy comparable to the natural ligand capsaicin, in rats operated with permanent bilateral carotid artery occlusion (BCAO), the animal model of stroke-related dysphagia. The ST-6631 antedrug properties have shown rapid metabolism by the hepatic S9 enzymatic fractions, and also shown extremely limited systemic bioavailability in blood circulation after the oral administration in vivo to rats. Furthermore, ST-6631 has been described to possess minimal pungency and irritancy in behavioral sensory assessments in awake rats. ST-6631 has been revealed to provide only a modest form of depolarization in rat sensory dorsal root ganglion (DRG) neurons. In addition, ST-6631 moderately activates the TRPV1 current, characterized by slower but long-lasting waveforms, in the channel-expressing Chinese hamster ovary (CHO) cells. Hence, the present study collectively highlights the pharmaceutically desired product profile of ST-6631, achieving TRPV1 agonism with minimal adverse effects, in clear contrast to the noxious reference ligand, capsaicin.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70243"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Pharmacology Education Through Collaborative Innovation: The Evolution and Future of PRORENATA at an Engineering-Based Medical Program.","authors":"Megan A Lim, Diamond Coleman, Noah Nigh, Chester Brown, Jessica Jia-Wen Saw, Noelle Kwan, Lisan Smith","doi":"10.1002/prp2.70234","DOIUrl":"10.1002/prp2.70234","url":null,"abstract":"<p><p>Carle Illinois College of Medicine (CI MED), the first engineering-based medical program in the United States, approaches teaching medicine with an engineering innovation mindset. This approach is reflected in PRORENATA, a pioneering web application designed to address the challenge of incorporating longitudinal pharmacological concepts consistently throughout a curriculum. PRORENATA aims to alleviate resource burden and maximize the learning of pharmacologic concepts through concept mapping. A pilot version of PRORENATA was launched in 2023 and demonstrated general usability. This report shares the design and initial implementation of PRORENATA, a novel web-based medical educational resource to support medical student learning of pharmacology and its clinical applications. Following PRORENATA's pilot, a collaborative effort was established with MedTerms, another developing medical education resource, to further enhance PRORENATA. MedTerms, created by the National Center for Supercomputing Applications (NCSA) at the University of Illinois Urbana-Champaign, uses visualization design and an innovative software user interface buildout to facilitate learning of diseases from foundational principles. PRORENATA's distinguishing advantage is its foundational support by technical experts (designers, software engineers) and medical content experts (medical students, medical educators, medical specialists), ensuring content accuracy and relevance. Specifically, PRORENATA provides a visual organization of content in a tree-like structure, classifying content by class or disease states (e.g., hypertension, acute coronary syndrome, etc.). When the user clicks on specific drugs, more detailed information is revealed, including mechanism of action, key indication, common side effects, and contraindications. Each image within PRORENATA links to its source page. Ultimately, PRORENATA is a student-designed and created resource application to enhance pharmacology education.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70234"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid Recognition in Adhesion GPCRs: A Structural and Pharmacological Perspective.","authors":"Bethany Fleming, Abdul-Akim Guseinov, Irina G Tikhonova, Graeme Milligan, Nicole A Perry-Hauser","doi":"10.1002/prp2.70221","DOIUrl":"10.1002/prp2.70221","url":null,"abstract":"<p><p>Emerging evidence suggests steroids may act as generalizable ligands for adhesion GPCRs, a receptor class with considerable pharmacological potential. While most studies have focused on the ADGR'G' subfamily, recent cryo-EM structures of the androgens 5α-dihydrotestosterone (5α-DHT) and methenolone bound to ADGRD1 revealed a putative steroid-binding pocket and enabled the rational design of a selective synthetic agonist. This perspective considers the broader significance of these findings amid some debate about the reproducibility and physiological relevance of steroid binding to adhesion GPCRs, reviewing all structural evidence and presenting comparative docking and homology modeling to evaluate conserved features and the plausibility of a shared recognition mechanism.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70221"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}