Pharmacological Reports最新文献

{"title":"Current insights into the safety and adverse effects of methylphenidate in children, adolescents, and adults - narrative review.","authors":"Andrzej Silczuk, Aleksandra Lewandowska, Małgorzata Filip, Paweł A Atroszko, Jakub Podolec, Małgorzata Gałecka, Robert Madejek, Łukasz Czyżewski","doi":"10.1007/s43440-025-00763-0","DOIUrl":"https://doi.org/10.1007/s43440-025-00763-0","url":null,"abstract":"<p><p>Methylphenidate (MPH) is a central nervous system stimulant that is approved and widely used for the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It acts primarily by inhibiting the reuptake of dopamine and norepinephrine, thereby enhancing synaptic concentrations of these neurotransmitters and improving attention, impulse control, and wakefulness. Despite its well-established therapeutic efficacy, MPH is associated with a complex safety profile that necessitates careful consideration, particularly in long-term use and in populations with preexisting health conditions. Cardiovascular risks, including increased heart rate, elevated blood pressure, and, in rare cases, serious adverse events such as myocardial infarction, arrhythmias, and sudden cardiac death, have been reported. Psychiatric adverse effects, including anxiety, agitation, psychotic symptoms, and exacerbation of preexisting mood disorders, also warrant close monitoring. Additionally, MPH has the potential for misuse, abuse, and dependence, particularly due to its dopaminergic effects, which can contribute to reinforcement and addiction-related behaviors. This review synthesizes current evidence on the safety of MPH, with a focus on its impact on cardiovascular and psychiatric health, and addiction potential. Special attention is given to vulnerable populations, including children, adolescents, individuals with comorbid psychiatric or cardiovascular conditions, and those with a history of substance use disorders. Furthermore, sex and gender influence health outcomes, for MPH healthcare strategies have been addressed. Given these concerns, the necessity for rigorous patient monitoring, individualized risk assessment, and adherence to prescribing guidelines is emphasized to optimize therapeutic outcomes while minimizing risks. Clinical trial number: Not applicable.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early plasma changes of HIF-1 alpha, matrix metalloproteinases-2 and - 9, and tissue inhibitor of matrix metalloproteinase-1 in patients with infantile hemangiomas treated with propranolol.","authors":"Małgorzata Kowalska, Olga Martyna Koper-Lenkiewicz, Joanna Kamińska, Wojciech Dębek, Adam Hermanowicz, Ewa Matuszczak","doi":"10.1007/s43440-025-00762-1","DOIUrl":"https://doi.org/10.1007/s43440-025-00762-1","url":null,"abstract":"<p><strong>Background: </strong>Infantile hemangiomas (IH) are the most prevalent benign vascular tumors diagnosed in the pediatric population. Propranolol, a nonselective beta-adrenergic receptor antagonist, is the first-line treatment for IH. In this study, we aimed to assess the changes in plasma levels of HIF-1α, MMP-2, MMP-9, and TIMP-1 in patients with IH before and after one month of propranolol treatment.</p><p><strong>Methods: </strong>Twenty children with IH and sixteen control subjects, admitted to the Department of Pediatric Surgery and Urology for elective inguinal hernia surgery, were included in this study. Blood plasma samples were obtained twice from the IH group (before and one month after initiating propranolol treatment) and once from the healthy control group.</p><p><strong>Results: </strong>Patients treated with propranolol exhibited higher levels of MMP-2 both before (p = 0.0008) and after (p = 0.0006) treatment compared to the control group. The control group had higher levels of MMP-9 than the study group before propranolol treatment (p = 0.0267), but MMP-9 levels increased significantly after propranolol treatment in the study group (p = 0.0281). Plasma levels of TIMP-1 were considerably higher in the study group both before (p = 0.0097) and after (p = 0.0013) propranolol treatment compared to the control group. Additionally, HIF-1α levels were higher in the study group and showed an upward trend following propranolol treatment compared to the control group (p = 0.0114).</p><p><strong>Conclusions: </strong>This study provides insight into the plasma levels of MMP-2, MMP-9, TIMP-1, and HIF-1α involved in the involution of infantile hemangiomas during the early stage of propranolol treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral tests to assess short- and long-lasting sensorimotor deficits following transient focal cerebral ischemia in rodents.","authors":"Enrique García-Alfonso, Jeney Ramírez-Sánchez, Maylin Wong-Guerra, Luis Arturo Fonseca-Fonseca, Yanay Montano-Peguero, Daniela Risco-Acevedo, Yanier Núñez-Figueredo","doi":"10.1007/s43440-025-00747-0","DOIUrl":"https://doi.org/10.1007/s43440-025-00747-0","url":null,"abstract":"<p><p>Cerebrovascular diseases are highly lethal and disabling events. Stroke is most commonly modeled using focal ischemia, of which middle cerebral artery occlusion (MCAO) is widely employed. Reproducible and reliable animal models are crucial for studying the pathophysiology of diseases and the evaluation of therapeutic candidates. However, despite showing efficacy in experimental studies, neuroprotective approaches have failed to translate into clinical benefit so far. A key measure to improve preclinical stroke research is the inclusion of functional endpoints intended to cover a wide range of parameters. The selection of appropriate tests is a critical issue and a challenging task, given the many variables to be considered. These variables include the experimental species, strain, sex, age, occlusion method and duration, infarct size and location, and degree of collateral irrigation, operational costs, among others. The focus of this review is on the behavioral tests most commonly used to identify neurological alterations associated with sensorimotor deficits following transient cerebral ischemia in rats and mice. Commonly used tests include the neurological score, the adhesive removal test, the hanging wire test, the corner test, the cylinder test, and the rotarod test. Functional endpoints must be included in preclinical testing, including sensorimotor and cognitive function, given the variable recovery rates of specific neurological functions. Importantly, screening for sensorimotor function prior to cognitive testing ensures accurate conclusions and helps identify the best specific conditions with minimal confounding by neurological abnormalities. Behavioral outcomes allow assessment of the severity, persistence, or recovery of post-ischemic injury over time.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Marizomib in the therapy of brain tumors-how far did we go and where do we stand?","authors":"Magdalena Kusaczuk, Wiktoria Monika Piskorz, Julia Domasik","doi":"10.1007/s43440-025-00755-0","DOIUrl":"https://doi.org/10.1007/s43440-025-00755-0","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of muscarinic and mGlu receptors modulators on MK-801-induced impairments in NO-dependent processes both in vitro and in vivo.","authors":"Grzegorz Burnat, Michał Santocki, Leszek Kalinowski, Joanna M Wierońska","doi":"10.1007/s43440-025-00752-3","DOIUrl":"https://doi.org/10.1007/s43440-025-00752-3","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is a mental disorder with multifactorial etiology including positive, negative and cognitive symptoms. Nitric oxide (NO֗)-related biochemical pathways significantly contribute to the disease's pathophysiology and subsequent antipsychotic treatment. Recently, metabotropic glutamatergic (mGlu) or muscarinic (M) receptors have been considered as potent antipsychotics with the potential to reverse cognitive symptoms. The aim of this study was to investigate how selected mGlu or muscarinic receptor ligands regulate the most important aspects of NO֗-related neurotransmission.</p><p><strong>Methods: </strong>In this study, MK-801-the tool compound that induces schizophrenia-related changes-was used alone or with mGlu or muscarinic receptor ligands. Positive allosteric modulators (PAM) of mGlu₂ (LY487379), mGlu₅ (CDPPB), M₁ (VU0357017) and M₄ (VU0152100) receptors were administered. cGMP levels, superoxide dismutase (SOD) activity, nitrite and GLT-1 s-nitrosilation processes were investigated in mouse brain and plasma samples, while oxidative stress was measured in vitro with the use of mouse or human astrocytic cell lines.</p><p><strong>Results: </strong>MK-801 did not change cGMP levels, while a decrease was observed in mice treated with VU0357017 or LY487379 in parallel. Increased SOD activity was observed in the cortex of MK-801-treated mice, and the compounds, with the exception of CDPPB, prevented this effect. The investigated compounds also prevented an MK-801-induced increase in plasma nitrite levels. GLT-1 protein was decreased after MK-801 treatment which was not evident in mice administered with muscarinic or mGlu ligands. GLT-1 S-nitrosilation was increased in all groups. In vitro studies revealed the potency of these compounds in counteracting MK-801-induced oxidative stress.</p><p><strong>Conclusions: </strong>The present data confirm that both mGlu and muscarinic receptor ligands may exert antipsychotic effects through biochemical pathways regulated by NO֗, in particular by decreasing oxidative stress indicators.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel 2-oxopyrrolidine derivative (LN-53) efficiently induces Nrf-2 signaling pathway activation in human epidermal keratinocytes.","authors":"Basak Ezgi Sarac, Laura Nissim, Dilara Karaguzel, Gokhan Arik, Shirin Kahremany, Edward E Korshin, Arie Gruzman, Cagatay Karaaslan","doi":"10.1007/s43440-025-00757-y","DOIUrl":"https://doi.org/10.1007/s43440-025-00757-y","url":null,"abstract":"<p><strong>Background: </strong>The skin is a pivotal organ that serves as a physical barrier, protecting the body from harmful substances such as pathogens, allergens, and other environmental irritants. Chronic inflammation in the skin, along with the anthropogenic effects, can cause reactive oxygen species (ROS) overproduction. Prolonged exposure to elevated ROS levels and inadequate antioxidant defenses in the skin can contribute to the onset of various skin disorders. The nuclear factor erythroid 2-related factor-2 (Nrf-2) signaling pathway plays a key role in enhancing antioxidant capacity by promoting the production of antioxidant and detoxifying molecules. Consequently, pharmacological activation of the Nrf-2 pathway may help restore the oxidant-antioxidant balance, thereby improving therapeutic outcomes for chronic skin disorders. This study aimed to investigate the potential effect of novel agent: (5-((4-(4-(methoxycarbonyl)-2-oxopyrrolidin-1-yl)phenyl)carbamoyl)benzene-1,2,3-triyl triacetate (LN-53), synthesized based on the structure of previously developed by our team lead compound SK-119, on Nrf-2 signaling pathway in human epidermal keratinocytes (HEKs) at mRNA and protein level.</p><p><strong>Methods: </strong>The cytotoxicity of LN-53 was evaluated by MTT, LDH, live/dead cell staining, and caspase-3,-8,-9 multiplex activity assays. Intracellular ROS production was assessed by DCFH-DA staining. The Nrf-2 gene was silenced by transient transfection using human Nrf-2 siRNA. Nrf-2 and related factors (heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase: quinone-1 (NQO1)) were evaluated at the mRNA level by qPCR and protein level in nuclear and cytosolic fractions by Nrf-2 activation assay and Western blot. The levels of inflammatory cytokines (IL-6 and IL-8) in supernatants were determined by ELISA.</p><p><strong>Results: </strong>Our results indicate that LN-53 effectively reduces intracellular ROS production triggered by tert-butyl hydroperoxide (TBHP), without leading to any noticeable cell damage. It promoted the nuclear translocation of Nrf-2 and induced the production of Nrf-2, HO-1, and NQO1 at both the mRNA and protein levels. LN-53-mediated alterations in antioxidant gene expressions were blocked by Nrf-2 knockdown. LN-53 treatment also suppressed the release of IL-6 and IL-8 cytokines mediated by TBHP exposure. Additionally, novel compound LN-53 was found to be more stable than the parent compound SK-119.</p><p><strong>Conclusion: </strong>LN-53 can effectively induce antioxidant mechanisms by promoting Nrf-2 nuclear translocation and suppressing ROS production in human epidermal keratinocytes. These data may suggest that LN-53 can contribute to maintaining redox balance and homeostasis in the skin.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the pharmacological mechanisms and therapeutic implications of galangin against neurological disorders.","authors":"Xueying Zhang, Guangcheng Zhong, Haike Wu","doi":"10.1007/s43440-025-00756-z","DOIUrl":"10.1007/s43440-025-00756-z","url":null,"abstract":"<p><p>Neurological disorders represent a leading cause of mortality and disability worldwide, encompassing a broad spectrum of prevalent conditions such as Alzheimer's disease, epilepsy, and stroke. In recent years, natural compounds have garnered increasing attention as potential therapeutic and preventive agents for neurological disorders. Galangin, a naturally occurring flavonoid primarily derived from Alpinia officinarum Hance, exhibits diverse biological properties, including notable neuroprotective, anti-tumor, and anti-inflammatory effects. Emerging evidence indicates that galangin exerts significant neuroprotective effects through multiple mechanisms. This review systematically summarizes the in vivo metabolism and pharmacokinetics of galangin, elucidates its mechanism of action, and highlights recent advances in its application for neurological disorders. Furthermore, the prospect of nanodrug carriers for enhancing the therapeutic efficacy of galangin is explored. Additionally, this review addresses the current research limitations and outlines future research directions to provide a theoretical foundation for its clinical application in neurological disorders. Collectively, the findings underscore the extensive pharmacological properties and therapeutic potential of galangin, highlighting its promise as a novel candidate for the treatment and prevention of neurological disorders and warranting further in-depth investigation and development.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The application of telmisartan in central nervous system disorders.","authors":"Wei Quan, Shui-Xian Zhang, Xu-Yang Zhang, Xi Chen, Chao Yang, Zhi-Yu Li, Rong Hu","doi":"10.1007/s43440-025-00737-2","DOIUrl":"https://doi.org/10.1007/s43440-025-00737-2","url":null,"abstract":"<p><p>Telmisartan, a well-established antihypertensive drug, has shown promising therapeutic potential for a variety of central nervous system (CNS) disorders. This review outlines the fundamental characteristics of telmisartan, focusing on its dual pharmacological effects as an angiotensin II type 1 receptor (AT1R) antagonist and a peroxisome proliferator-activated receptor (PPAR) γ activator. These mechanisms underpin its neuroprotective and anti-inflammatory effects, which are essential to its therapeutic benefits in CNS diseases. Telmisartan modulates key cellular components of the CNS, including microglia, astrocytes, oligodendrocytes, vascular endothelial cells, and neurons, thereby offering protection against neuroinflammation, oxidative stress, and neuronal damage. We summarize telmisartan's efficacy in addressing a range of neurological conditions, such as stroke, traumatic brain injury, dementia, Parkinson's disease, demyelinating diseases, psychiatric disorders, and gliomas. By targeting multiple pathways involved in these disorders, telmisartan demonstrates potential as both an adjunctive and standalone therapy. Its ability to attenuate neuroinflammation and promote cellular repair highlights its versatility in CNS disease management. This review underscores the potential of telmisartan as a valuable therapeutic option for CNS disorders, warranting continued exploration to optimize its clinical application.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of curcumin on vascular smooth muscle cells: implications for health and disease.","authors":"Majid Shohrati, Farshad Abedi, Mahdi Bagheri, Amirhossein Sahebkar","doi":"10.1007/s43440-025-00744-3","DOIUrl":"https://doi.org/10.1007/s43440-025-00744-3","url":null,"abstract":"<p><p>Vascular smooth muscle cells (SMCs) are pivotal in regulating vascular tone and integrity. Their dysregulation significantly contributes to the pathophysiology of cardiovascular ailments, including atherosclerosis, blood pressure, and vascular remodeling. Curcumin, a polyphenol with a natural origin in turmeric, exhibits promising therapeutic properties due to its remarkable anti-inflammatory, antioxidant, and antiproliferative characteristics. This review aims to assess the effects of curcumin on vascular SMC behavior, encompassing its impact on proliferation, migration, phenotypic switching, and extracellular matrix remodeling. The underlying molecular mechanisms are highlighted, particularly curcumin's modulation of signaling pathways such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and nuclear transcription factor E2-related factor-2 (Nrf2) signaling pathways, as well as its ability to decrease oxidative stress and inflammatory cytokine generation. Furthermore, we evaluate the implications of the results for vascular health and disease, emphasizing curcumin's potential to prevent or mitigate atherosclerosis, restenosis, and hypertension. Despite promising preclinical evidence, challenges related to curcumin's bioavailability and clinical translation remain.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone-9: a novel inhibitor of the JAK-STAT pathway with potent anti-cancer effects in triple-negative breast cancer cells.","authors":"Song-Hee Lee, Haeri Lee, Yong-Jin Kwon, Seul-Ki Kim, Eun-Bi Seo, Jie Ohn Sohn, Byung-Hak Kim, Jung-Youl Park, Sang-Kyu Ye","doi":"10.1007/s43440-025-00721-w","DOIUrl":"10.1007/s43440-025-00721-w","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains the leading cause of cancer incidence and mortality among women worldwide, with triple-negative breast cancer (TNBC) posing significant treatment challenges. The dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway contributes to tumor progression, making it a potential therapeutic target. Chalcones, known for their diverse biological activities, including anti-cancer effects, hold promise for drug development. This study explores the anti-cancer activity of (E)-4-(3-(2-(benzyloxy)-6-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid (chalcone-9), a novel chalcone derivative.</p><p><strong>Methods: </strong>The cytotoxic effects of chalcone-9 were evaluated in breast cancer cell lines, including TNBC lines MDA-MB-231 and MDA-MB-468. Western blotting and qRT-PCR were used to analyze the impact on JAK1, JAK2, STAT1, and STAT3 activation and their downstream gene expression. In silico molecular docking analysis was conducted to determine whether chalcone-9 can interact with JAK1 and JAK2. A wound healing assay was used to observe the effect of chalcone-9 on tumor cell migration, and flow cytometry was employed to analyze whether chalcone-9 inhibits tumor cell cycle progression and induces apoptosis. The expression of apoptosis markers was also assessed.</p><p><strong>Results: </strong>Chalcone-9 exhibited dose-dependent cytotoxicity in breast cancer cell lines, with TNBC cells showing higher sensitivity. Chalcone-9 effectively inhibited the activation of JAK1, JAK2, STAT1, and STAT3, outperforming conventional JAK/STAT inhibitors. The structure of chalcone-9 was confirmed to stably interact with JAK1 and JAK2 proteins. It also suppressed STAT1 and STAT3 target gene expression, reduced tumor cell migration, and induced apoptosis, as evidenced by PARP and caspase cleavage and decreased survivin levels.</p><p><strong>Conclusions: </strong>Chalcone-9 demonstrates significant anti-cancer activity, particularly against TNBC. By targeting the JAK/STAT pathway and promoting apoptosis, chalcone-9 emerges as a promising therapeutic candidate for aggressive breast cancers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"761-774"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812120","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}