Pharmaceuticals最新文献

{"title":"Unexplored Bioactive, Antioxidant, Antimicrobial, and Nematicidal Potential of the Flowers, Leaves, and Roots of 'Yellow Chicory' (<i>Hypochaeris sessiliflora</i>).","authors":"Elena Coyago-Cruz, Gabriela Méndez, Johana Zúñiga-Miranda, Alejandro Porras, Carlos Barba-Ostria, Ivanna Sarabia, Linda P Guamán, Celina Coello, Jorge Heredia-Moya, Blanca Naranjo, María Claudia Segovia-Salcedo","doi":"10.3390/ph19081314","DOIUrl":"10.3390/ph19081314","url":null,"abstract":"<p><p>This exploratory study compared the flowers, leaves, and roots of <i>Hypochaeris sessiliflora</i> to evaluate physicochemical properties, bioactive compounds, in vitro chemical antioxidant activity, antimicrobial activity, and locomotion-disrupting effects on <i>Caenorhabditis elegans</i>. Bioactive compounds were determined by liquid chromatography; in vitro chemical antioxidant activity by microplate spectrophotometry; antimicrobial activity against a range of ATCC and multidrug-resistant microorganisms; and locomotion-disrupting effects on <i>Caenorhabditis elegans</i>. The results revealed significant differences between plant organs. The leaves contained the highest concentrations of calcium (1163.1 mg/100 g DW), potassium (3256.6 mg/100 g DW), vitamin C (39.2 mg/100 g DW), organic acids (1213.5 mg/100 g DW), and total quantified chlorophylls (89.0 mg/100 g DW). The flowers had the highest levels of total quantified carotenoids (152.1 mg/100 g DM) and total quantified phenolic compounds (12,341.1 mg/100 g DM). They exhibited the highest in vitro chemical antioxidant activity, as measured by the ABTS assay (6.1 mmol TE/100 g DW). The extracts exhibited antimicrobial activity that depended on the plant organ and the microorganism tested, with the root extract being the most active against <i>Staphylococcus epidermidis</i> (MIC = 8.2 mg/mL). No activity was detected against <i>Candida</i> species or against multidrug-resistant bacteria under the experimental conditions used. Furthermore, the extracts under the experimental conditions used did not significantly alter <i>C. elegans'</i> locomotion. Overall, this study provides baseline evidence of the organ-specific chemical composition and biological properties of <i>H. sessiliflora</i>, supporting further investigation of the compounds responsible for the observed in vitro chemical antioxidant and selective and antimicrobial activities.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Faricimab 6 mg Versus Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Protocol-Standardised In Silico Study.","authors":"Georgios D Panos","doi":"10.3390/ph19081316","DOIUrl":"10.3390/ph19081316","url":null,"abstract":"<p><p><b>Background</b>: Faricimab 6 mg and aflibercept 8 mg permit extended treatment intervals in neovascular age-related macular degeneration (nAMD), but their pivotal programmes used different loading and maintenance schedules. This study compared treatment burden under the same loading and treat-and-extend protocol and included an exploratory longitudinal analysis of published aggregate visual and anatomical outcomes. <b>Methods</b>: Treatment-specific Dirichlet distributions represented persistent Q8W, Q12W and Q16W capability. Both treatments received injections at weeks 0, 4, 8 and 16, followed by identical four-week extensions from Q8W to Q16W. The primary analysis comprised 30,000 evidence draws, 100,000 paired virtual eyes, a 1.5-million-pair scenario grid and a nested five-million-pair probabilistic analysis. Exploratory multilevel meta-regressions estimated BCVA and change in retinal thickness through week 52; IRF, SRF and complete retinal dryness were analysed separately. <b>Results</b>: Mean injections with faricimab and aflibercept 8 mg were 7.255 and 7.212 at week 52 and 11.522 and 11.144 at week 104. The nested 104-week difference was -0.393 injection (95% uncertainty interval -0.682 to -0.107), but broad source-weight uncertainty included no difference and credible source analyses changed the direction of the contrast. Exploratory week-52 BCVA gains were 5.65 and 6.29 letters, respectively; the difference was 0.64 letter (95% uncertainty interval -1.41 to 2.70) and should be interpreted in the context of three aflibercept 8 mg study families. The expanded retinal-thickness sensitivity model estimated changes of -171.8 and -147.2 micrometres, while the between-treatment direction varied in the three-dose-only analysis. Complete retinal dryness was projected in 57.0% and 69.0% of eyes, respectively, based on three study families per treatment. <b>Conclusions</b>: Use of the same protocol predicted essentially equal one-year burden and a small two-year fixed-weight difference that varied across source choices. The exploratory longitudinal projections, informed by three independent aflibercept 8 mg study families at one year, provide supportive context for the visual and anatomical findings but should be interpreted as hypothesis-generating rather than confirmatory.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic and Preliminary Safety Profiling of a Multicomponent Natural Product-Based Injectable Formulation Targeting Skin Aging-Related Pathways: A Network Pharmacology and Single-Dose Toxicity Study.","authors":"Ji Hye Hwang, Chul Jung","doi":"10.3390/ph19081317","DOIUrl":"10.3390/ph19081317","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Skin aging involves interconnected inflammatory, oxidative, hormonal, extracellular matrix (ECM), and cellular senescence-related mechanisms, supporting the need for multitarget approaches. This study aimed to evaluate the effects of a multicomponent natural product-based injectable formulation developed in Korean medicine practice, Dong-An Pharmacopuncture (DAP), on skin aging-related pathways. <b>Methods:</b> A network pharmacology approach was used to identify the active compounds, predicted molecular targets, and signaling pathways associated with DAP. Sixty-two active compounds from 11 constituent materials were screened, and 70 final targets were identified using STITCH-based prediction, intersection with GeneCards-derived skin aging-related targets, and quality filtering. <b>Results:</b> Herb-compound-target network analysis yielded 225 compound-target interactions across 292 edges. Protein-protein interaction analysis identified a highly connected network with 1,334 edges, and hub analysis converged on 10 core targets: <i>TNF</i>, <i>IL6</i>, <i>ESR1</i>, <i>TP53</i>, <i>AKT1</i>, <i>PPARG</i>, <i>EGFR</i>, <i>PTGS2</i>, <i>CASP3</i>, and <i>PPARA</i>. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses identified four major mechanistic axes: inflammatory and oxidative stress regulation, hormonal skin homeostasis, tissue repair and ECM remodeling, and cellular senescence-related regulation. Because DAP is administered by injection, a Good Laboratory Practice-compliant single-dose subcutaneous toxicity study was additionally conducted in Sprague-Dawley rats, which showed no mortality, abnormal clinical signs, or histopathological findings attributable to DAP at 1.0 mL/head. <b>Conclusions:</b> The findings in this study provide a systems-level framework for the predicted multitarget mechanisms of DAP in skin aging-related pathways and support the need for further experimental validation of its predicted mechanisms and repeated-dose safety.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G Protein-Mediated Allosteric Modulation of Ligand Binding in Class A GPCRs: Receptor-Ligand-Transducer Ensembles in Disease and Drug Discovery.","authors":"Yukiko Kurihara, Hiroki Kurihara","doi":"10.3390/ph19081312","DOIUrl":"10.3390/ph19081312","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are dynamic allosteric proteins whose signaling properties are governed by reciprocal communication between extracellular ligand-binding sites and intracellular transducer interfaces. Although classical pharmacological models established the concept that ligand binding and G protein coupling are thermodynamically linked, recent structural, biophysical, and computational studies have revealed a far more complex picture in which GPCRs exist as ensembles of interconverting conformational states. Accumulating evidence indicates that G proteins function not only as downstream signaling effectors but also as endogenous allosteric modulators. By reshaping receptor conformational landscapes, G protein coupling can influence the structure and dynamics of orthosteric ligand-binding pockets, thereby regulating ligand affinity, binding kinetics, and receptor selectivity. These findings support a bidirectional model of GPCR signaling in which information is transmitted not only from ligand-binding sites to intracellular signaling partners but also in the reverse direction through receptor-wide allosteric networks. Disease-associated mutations of endothelin A receptor (ETAR) provide in vivo evidence that structural perturbations located far from orthosteric ligand-binding sites can alter ligand recognition through long-range allosteric communication. In addition, emerging studies of positive allosteric modulators demonstrate the therapeutic potential of selectively stabilizing ligand-receptor-G protein complexes. These observations suggest that ligand recognition, receptor activation, and transducer coupling should be viewed as integrated properties of a dynamic receptor-ligand-transducer ensemble. This perspective provides a conceptual framework that links classical GPCR pharmacology, structural biology, disease mechanisms, and next-generation drug discovery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis-Driven Drug Repurposing with a Self-Nanoemulsifying Delivery System for Parkinson's Disease.","authors":"Kunal Verma, Jaskiran Kaur, Mohit Kumar, Ankit Awasthi, Dinesh Kumar, Neeraj Choudhary, Emad M Abdallah","doi":"10.3390/ph19081311","DOIUrl":"10.3390/ph19081311","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The aim of the present study was to investigate the mechanisms in Parkinson's disease (PD), a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, aggregation of α-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, gut dysbiosis, and blood-brain barrier (BBB) impairment. Although there are several approved therapies that have been developed, their aqueous solubility, oral bioavailability, first-pass metabolism, and inability to penetrate the BBB make them less effective over time. This review is intended to critically analyze the potential of self-nanoemulsifying drug delivery systems (SNEDDSs) as a pathogenesis-related approach to enhance the delivery and therapeutic activity of repurposed drugs and conventional drugs for PD. <b>Methods</b>: A comprehensive literature search was conducted to address the pathogenic mechanisms of PD, the deficiencies of current pharmacotherapy, recent developments in SNEDDS formulation strategies and their application in improving oral bioavailability, lymphatic transport, BBB penetration and targeted brain delivery. A special focus was dedicated to drug repurposing, functionalized SNEDDSs, PEGylation, and gut-brain axis modulation. <b>Results</b>: SNEDDSs significantly enhance the water solubility, stability, intestinal absorption and systemic exposure of poorly water-soluble therapeutic agents and, to a certain extent, lymphatic uptake to avoid first-pass metabolism. These systems include improved brain delivery, decreased pharmacokinetic variability, and prolonged drug levels within the therapeutic range. Moreover, SNEDDSs can be used to deliver multiple molecules that are found to be neuroprotective, antioxidant, anti-inflammatory and probiotic, all at once, which can act on multiple pathogenic mechanisms associated with PD. Functionalized and PEGylated SNEDDSs add further to formulation stability, extend systemic circulation and increase efficiency of brain targeting. <b>Conclusions</b>: SNEDDSs are a promising translational nanomedicine platform for enhancing the effectiveness of conventional and repurposed therapeutics in PD, which address key pharmacokinetic and biological challenges. The next generation of oral therapies with targeted surface engineering, precision drug repurposing and clinical validation will be expected to bring about a faster advancement of drugs that can alter the course of disease rather than giving only symptomatic relief.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13517005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated AI-Driven Discovery of MAPK3 Inhibitors for Oral Inflammatory and Proliferative Diseases.","authors":"Muhammad Ishfaq, Shahi Jahan Shah, Imran Khalid, Mashail M M Hamid, Muhammad Zahir Kota, Abdul Ahad Ghaffar Khan, Mohammed Ibrahim, Samuel Ebele Udeabor, Abosofyan Salih Atta Elfadeel Mohamed Salih, Chidozie Ifechi Onwuka","doi":"10.3390/ph19081309","DOIUrl":"10.3390/ph19081309","url":null,"abstract":"<p><p><b>Background</b>: Mitogen-activated protein kinase 3 (MAPK3/ERK1) plays a central role in cellular proliferation, inflammation, apoptosis, and survival signalling and has been implicated in oral squamous cell carcinoma (OSCC), periodontitis, oral lichen planus, and other chronic oral inflammatory diseases. The present study employed an integrated computational workflow combining machine learning (ML)-based quantitative structure-activity relationship (QSAR) modelling, molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, and MM-GBSA analysis to identify and characterise potent MAPK3 inhibitors. <b>Methods</b>: A curated dataset of 907 experimentally validated MAPK3 inhibitors was retrieved from the ChEMBL database and processed using molecular descriptors and Morgan fingerprints. Multiple ML algorithms were evaluated under scaffold-based validation, with Light Gradient Boosting Machine (LightGBM) demonstrating the best predictive performance. <b>Results</b>: The final model achieved strong classification capability with ROC-AUC values of 0.898 and 0.926. Feature importance analysis revealed that local structural motifs captured by fingerprint descriptors played dominant roles in MAPK3 inhibitory activity. The top-ranked compounds were subjected to molecular docking, where compounds 58324148 and 137531515 exhibited strong binding affinities of -11.9 and -11.0 kcal/mol, respectively. DFT calculations demonstrated favourable electronic properties with low HOMO-LUMO energy gaps, while MD simulations confirmed stable receptor-ligand interactions throughout 200 ns trajectories. MM-GBSA analysis further supported strong binding stability dominated by van der Waals interactions. <b>Conclusions</b>: Overall, the integrated computational framework successfully identified promising MAPK3 inhibitor candidates with potential therapeutic relevance for oral inflammatory and proliferative diseases.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Consensus Machine Learning and Structure-Based Workflow for the Discovery of Novel Tankyrase 1 Inhibitors.","authors":"Marina Bilotta, Adriana Gargano, Roberta Rocca, Valentina Maggisano, Stefania Bulotta, Stefano Alcaro","doi":"10.3390/ph19081310","DOIUrl":"10.3390/ph19081310","url":null,"abstract":"<p><p><b>Background:</b> Tankyrase 1 (TNKS1) is a poly(ADP-ribose) polymerase involved in Wnt/β-catenin signaling, telomere maintenance, and genomic stability, making it an attractive therapeutic target in oncology. This study aimed to develop and apply an integrated computational workflow to identify novel TNKS1 inhibitor candidates. <b>Methods:</b> A curated dataset of experimentally validated TNKS1 inhibitors and property-matched DUD-E decoys was used to develop a <i>consensus</i> supervised machine learning (ML) model prioritization framework for ligand-based virtual screening, integrating Morgan fingerprints with three complementary classifiers. The model screened more than 700,000 compounds, and prioritized hits were evaluated by structure-based virtual screening (SBVS), Prime MM-GBSA binding free-energy refinement, and 500 ns molecular dynamics simulations (MDs). The top candidates were subsequently tested in an in vitro TNKS1 enzymatic inhibition assay. <b>Results:</b> The <i>consensus</i> ML framework prioritized 670 compounds, yielding five candidates for experimental testing. <b>Compound 3</b> displayed the most favorable computational profile and was experimentally confirmed as a TNKS1 inhibitor candidate, exhibiting approximately 80% TNKS1 inhibition at 0.1 μM, whereas the remaining candidates showed only limited activity. <b>Conclusions:</b> The proposed workflow efficiently reduced a large chemical space to a focused set of TNKS1 inhibitor candidates while substantially reducing the experimental screening burden. <b>Compound 3</b> represents a promising starting point for future structure-activity relationship studies and lead optimization in the context of TNKS1 inhibition. Moreover, this work highlights the value of integrating <i>consensus</i> ML, SBVS, and experimental validation to accelerate early-stage hit discovery for TNKS1 and other therapeutic targets.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Drug Monitoring and Adverse Drug Reactions: From Signal Detection to Prevention.","authors":"Engi Algharably, Ursula Gundert-Remy","doi":"10.3390/ph19081308","DOIUrl":"10.3390/ph19081308","url":null,"abstract":"<p><p>Optimizing pharmacotherapy is a central goal of clinical pharmacology [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siweixizangmaoru Decoction Alleviates Rheumatoid Arthritis by Enhancing Pol β-Mediated Attenuation of DNA Damage and Suppression of cGAS/STING/NF-κB/NLRP3-Associated Pyroptosis.","authors":"Xiaotong Chu, Xiao Chen, Yanxiang Yuan, Yanfei Niu, Wentao Zhou, Yiming Cui, Yongyue Pan, Haifeng Liu, Zhuoma Dongzhi, Shan Huang, Bin Li","doi":"10.3390/ph19081302","DOIUrl":"10.3390/ph19081302","url":null,"abstract":"<p><p><b>Objective:</b> Siweixizangmaoru decoction (SXD), a classical Tibetan prescription documented in the medical text <i>Four Medical Tantras</i>, has shown therapeutic activity in experimental rheumatoid arthritis (RA). However, its candidate active constituents and underlying mechanisms remain unclear. <b>Methods:</b> In this study, serum-absorbed constituents following SXD administration were profiled using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), and network pharmacology was employed to identify core targets and candidate active constituents of SXD against RA. Candidate active constituents were further screened using cell-based assays, and the selected constituents were quantified using HPLC fingerprint analysis. Both in vivo (CIA rat model) and in vitro (RAW264.7 pyroptosis model) systems were used to investigate the pharmacological effects and mechanisms of SXD. <b>Results:</b> A total of 11 absorbed constituents were identified in the serum of SXD-treated rats, and four preliminary candidate active constituents, including chebulagic acid, kaempferol, gentiopicroside, and berberine, were screened. The combined in vivo and in vitro results showed that SXD attenuated RA progression and reduced inflammatory cytokine levels in rat serum and cell culture supernatants. At the molecular level, SXD increased Pol β expression and reduced DNA damage markers, cytosolic dsDNA accumulation, and cGAS/STING-, NF-κB-, and NLRP3-associated signaling. Pol β knockdown partially reduced the effects of SXD. <b>Conclusions:</b> These findings support the partial involvement of Pol β-associated processes in the anti-arthritic effects of SXD.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clascoterone in the Treatment of Acne Vulgaris: A Narrative Review.","authors":"Sara Shefa, Jagoda Szwach, Anna Karwowska, Aleksandra Wojno, Magdalena Łyko","doi":"10.3390/ph19081304","DOIUrl":"10.3390/ph19081304","url":null,"abstract":"<p><p>Acne vulgaris is one of the most prevalent dermatological conditions, affecting up to 85% of individuals aged 11-30 years. Clascoterone cream is the first topical androgen receptor inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of acne vulgaris in patients aged 12 years and older, and the first agent in this class approved for use in both male and female patients. The aim of this narrative review is to summarize the current evidence regarding the efficacy, safety profile, and potential future applications of clascoterone in the treatment of acne vulgaris. A comprehensive literature search was conducted in PubMed/MEDLINE and ClinicalTrials.gov databases up to April 2026. Search terms included \"clascoterone,\" \"cortexolone 17α-propionate,\" and \"androgen receptor inhibitor acne.\" Eligible publications included randomized controlled trials, meta-analyses, open-label extension studies, retrospective analyses, case reports, and relevant review articles published in English. Clinical trial registries and regulatory agency announcements were also searched for ongoing studies and recent approval decisions. Phase 3 trials and meta-analyses demonstrate that twice-daily application of clascoterone 1% cream significantly reduces inflammatory and non-inflammatory lesion counts compared to vehicle, with efficacy sustained up to 12 months of treatment. The safety profile is favorable, with adverse events limited predominantly to mild and transient local skin reactions. Subgroup analyses have shown no significant sex-related differences in efficacy or safety, and the safety profile appears comparable between adolescents and adults. In an exploratory pooled subgroup analysis, lesion-count reductions were greater in adults than in adolescents, whereas the adjusted between-group comparison of IGA success was not statistically significant. Because no formal treatment-by-age interaction test was reported, these findings should be considered hypothesis-generating. Emerging but still incomplete data suggest potential applications in androgenetic alopecia and mild hidradenitis suppurativa. Clascoterone represents a novel addition to the therapeutic armamentarium for acne vulgaris, offering a unique mechanism of action with a favorable safety profile. Further research is warranted to establish its role in combination therapies and in other androgen-dependent dermatoses.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}