Pharmacology Research & Perspectives最新文献

{"title":"Metformin Inhibits Ferroptotic Cell Death by Suppressing Cysteine Deprivation-Induced Mitochondrial Dysfunction.","authors":"Se-Kyeong Jang, Selim Kim, Gyeongmi Kim, Jungil Hong, In-Chul Park, Hyeon-Ok Jin","doi":"10.1002/prp2.70330","DOIUrl":"10.1002/prp2.70330","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has emerged as a promising therapeutic strategy for cancer. Metformin, a widely used biguanide antidiabetic drug, has recently been reported to induce ferroptosis and exert anticancer effects in various malignancies. However, metformin or its analogue phenformin did not induce ferroptotic cell death in H1299 non-small cell lung cancer cells and HEYA8 ovarian cancer cells for up to 24 h. Instead, both drugs attenuated cysteine deprivation-induced ferroptotic cell death, which also appeared to involve necroptotic signaling. This effect was accompanied by reductions in reactive oxygen species generation, iron accumulation, and lipid peroxidation at both the cellular and mitochondrial levels. Notably, metformin and phenformin suppressed cysteine deprivation-induced mitochondrial membrane hyperpolarization and increased oxygen consumption, suggesting suppression of mitochondrial bioenergetic activity associated with cysteine deprivation-induced ferroptosis. Cysteine deprivation markedly reduced glutathione (GSH) levels and glutathione peroxidase 4 (GPX4) expression. Although metformin alone also reduced intracellular GSH levels, metformin did not restore GSH levels or GPX4 expression under cysteine deprivation despite suppressing ferroptosis, indicating that its anti-ferroptotic effects are independent of the canonical GSH-GPX4 axis. Collectively, these findings underscore that the use of biguanides should be carefully considered when applying cysteine deprivation-based ferroptosis-inducing strategies in cancer.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 5","pages":"e70330"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128370","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":"Improving Medication Management in Indonesian Aged Care Homes: Research Priority Setting With Stakeholders.","authors":"Yulisna Mutia Sari, J Simon Bell, Surya Adhi, Uswa Alhamid, Esthika Dewiasty, Annisa Dhanira, Clara M Kusharto, Evi Dwi Novriany, Dion Notario, Imran Pambudi, Rocksy Situmeang, Sri Soenarti, M Rizky Widodo, Grace Wangge","doi":"10.1002/prp2.70328","DOIUrl":"10.1002/prp2.70328","url":null,"abstract":"<p><p>Indonesia and other Southeast Asian nations are experiencing rapidly aging populations. The Indonesian Government recently announced a national initiative of aged care homes to support older people not able to live independently or receive family care. Medication-without-harm is the topic of the World Health Organization Third Global Patient Safety Challenge. The objective of this study was to prioritize research questions for improving medication management in public and private aged care homes in Indonesia. In April 2025, a 20-person expert consensus panel was convened comprising general practitioners, geriatricians, neurologists, nurses, pharmacists, physiotherapists, nutritionists, public health practitioners, aged care home managers, Ministry of Health representatives, ASEAN organization representatives, and a family caregiver. The panel used modified nominal group technique to identify and prioritize research for improving medication management in aged care homes in Indonesia. The panel identified 47 research priorities that were consolidated into 15 policy and 20 practice priorities for voting. The highest ranked policy priorities focused on necessary regulations and clinical guidelines; essential medication lists for older people; and policies to support development and use of drug formulations acceptable for residents of aged care homes. The highest ranked practice priorities emphasized digital health technologies; medication safety monitoring; and enhancing communication among families, aged care home staff, and prescribers. The findings lay the groundwork for a culturally- and context-specific research roadmap for improving medication management in Indonesian aged care homes. This will guide researchers and research funding organizations in aligning future studies with policy and practice priorities.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 5","pages":"e70328"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081766","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":"Evaluating the Impact of CYP1A2 Inhibition on the Pharmacokinetics of Savolitinib: A Phase 1 Open-Label Study.","authors":"Kowser Miah, Jitendar Reddy, Pradeep Sharma, Ike Igwegbe, Simon Nelson, Caitlin Muldoon, Ronald Goldwater, Karthick Vishwanathan","doi":"10.1002/prp2.70321","DOIUrl":"10.1002/prp2.70321","url":null,"abstract":"<p><p>Savolitinib is an oral, potent, selective CNS-penetrant MET-tyrosine kinase inhibitor that in vitro studies indicate is metabolized by cytochrome P450 (CYP) enzymes, including CYP1A2, and by non-CYP enzymes, such as aldehyde oxidase (AO). Savolitinib primary metabolites, M2 and M3, are formed mainly by CYP1A2 and AO, respectively. This Phase 1, open-label study evaluated the impact of CYP1A2 inhibition by fluvoxamine on the pharmacokinetics of savolitinib and its metabolites in 16 healthy male volunteers. Volunteers received a single oral dose of 300 mg savolitinib and, following a ≥ 10-day washout period, 50 mg twice-daily oral fluvoxamine for 6 days, with a single oral dose of 300 mg savolitinib co-administered on Day 5. Serial pharmacokinetic samples were collected during both study periods. Savolitinib, M2, and M3 were measured using high-performance liquid chromatography with tandem mass spectrometry. Systemic exposure of savolitinib increased by approximately 2-fold (maximum plasma concentration) and 3-fold (area under the plasma concentration-time curve from time 0 to infinity) when savolitinib was administered with fluvoxamine compared with savolitinib alone. Systemic exposure of M2 and M3 decreased and increased, respectively, when savolitinib was administered with vs. without fluvoxamine, while the ratio of M2/savolitinib was reduced and that of M3/savolitinib remained unchanged. These data suggest a significant drug-drug interaction between savolitinib and the strong CYP1A2 inhibitor, fluvoxamine, and that CYP1A2 is involved in the formation of M2, but not M3. No new safety concerns were observed when savolitinib was administered alone or with twice-daily fluvoxamine.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 5","pages":"e70321"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025814","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 Bile Acid Signaling Axis: Deciphering the Roles of FXR and TGR5 in Hepatic Steatosis, Fibrosis, and Cancer.","authors":"Jie Liu, Kui Sun, Hongmei Liu, Meiyang Zhu, Chunmeng Li, Yuqi He, Lin Qin","doi":"10.1002/prp2.70318","DOIUrl":"10.1002/prp2.70318","url":null,"abstract":"<p><p>Bile acids (BAs) serve not only as emulsifiers for lipid digestion but also as essential signaling molecules, governing various physiological and pathological processes through their interaction with the farnesoid X receptor (FXR) and the takeda G protein-coupled receptor 5 (TGR5). In recent years, the critical roles of FXR and TGR5 in ameliorating hepatic steatosis, modulating inflammatory responses, and regulating glucose and lipid metabolism, as well as in cholestasis, have gained significant recognition, positioning them as pivotal targets in liver disease research. This article offers a comprehensive review of the structural characteristics and physiological functions of both FXR and TGR5, highlighting their integral contributions to the pathogenesis and progression of various liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, and liver cancer. Additionally, it examines the latest advancements in the research and development of pharmacological agents targeting FXR and TGR5, encompassing both agonists and antagonists, and explores their potential clinical applications. A thorough understanding of the FXR and TGR5 signaling pathways will provide a critical theoretical foundation for the development of treatment strategies for liver diseases.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 5","pages":"e70318"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081774","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":"Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications.","authors":"Nora H J Alharbi","doi":"10.1002/prp2.70329","DOIUrl":"https://doi.org/10.1002/prp2.70329","url":null,"abstract":"<p><p>Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1's brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure (BP), lipid profile, obesity and major adverse cardiovascular event. Although the BP-lowering effect of GLP-1R agonists is well documented in clinical trials, the underlying molecular mechanisms remain incompletely defined, since most evidence comes from animal and in vitro models rather than human studies. This gap limits translating the clinical benefit into targeted, mechanism-based practice. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1R agonists, their effects on BP and how they exert their actions. Evidence indicates GLP-1R agonists produce a modest, consistent reduction in systolic blood pressure, heterogeneous across agents and confined to patients with elevated baseline BP, reflecting vascular, renal and anti-inflammatory mechanisms rather than a single pathway. Although animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1R agonists on BP regulation and their underlying mechanisms.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 5","pages":"e70329"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113102","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":"Drug-Induced Liver Injury During Treatment With Tocilizumab: A Case Report of an Atypical Pattern Lesion.","authors":"Louis-Edmond Barbaro, Nouha Ben Othman, Delphine Viard, Fanny Rocher, Elliot Ewig, Raja Mroue, Claire Amigues, Alexandre O Gérard","doi":"10.1002/prp2.70323","DOIUrl":"10.1002/prp2.70323","url":null,"abstract":"<p><p>Tocilizumab is an interleukin-6 (IL-6) receptor antagonist indicated for various rheumatologic conditions. While hepatotoxicity is a recognized adverse effect, it predominantly manifests as hepatocellular injury. We report a rare case of drug-induced liver injury (DILI) presenting with a cholestatic pattern and cholangitis features in a 75-year-old patient treated for giant cell arteritis. Following the third tocilizumab infusion, the patient developed jaundice and abdominal pain. Laboratory investigations revealed a cholestatic pattern of liver injury (ALT/ALP (R) ratio ≤ 2) with marked cholestasis. Imaging findings raised suspicion for cholangitis. After ruling out infectious, autoimmune, and metabolic aetiologies, a liver biopsy confirmed neutrophilic cholangitis and marked intrahepatic and sinusoidal cholestasis. Drug discontinuation, along with ursodeoxycholic acid treatment, led to clinical and biochemical resolution. This case is notable as tocilizumab-induced liver injury rarely presents with cholangitic features. The pathophysiology may involve the disruption of IL-6 signaling, which plays a pivotal role in maintaining biliary epithelial integrity. Clinicians should be vigilant for this atypical cholestatic presentation to ensure prompt drug withdrawal.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 5","pages":"e70323"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017609","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":"Development and Validation of an XGBoost-SHAP Model for Predicting Adverse Outcomes in Elderly Cardiovascular Patients With Polypharmacy: A Retrospective Cohort Study.","authors":"Kun Wang, Dandan Cao","doi":"10.1002/prp2.70293","DOIUrl":"10.1002/prp2.70293","url":null,"abstract":"<p><p>This study aims to develop and validate an interpretable machine learning model using Extreme Gradient Boosting (XGBoost) with SHapley Additive exPlanations (SHAP) analysis to predict adverse outcomes in elderly cardiovascular patients with polypharmacy. This retrospective cohort study included 1200 patients aged ≥ 65 years with cardiovascular disease and polypharmacy (≥ 5 medications) from The First Affiliated Hospital of Soochow University between January 2021 and December 2024. Data were split into training (60%), validation (20%), and test (20%) sets. The primary outcome was adverse drug events (ADEs); secondary outcomes included 30-day readmission, 90-day readmission, and 1-year mortality. XGBoost models were developed and compared with logistic regression, random forest, and support vector machine algorithms. Model interpretability was enhanced using SHAP values to identify key predictive features and their contributions. The cohort had a mean age of 76.34 ± 8.12 years, with 18.92% experiencing ADEs during follow-up. The XGBoost model demonstrated strong discriminative ability for ADE prediction (AUC 0.857, 95% CI: 0.790-0.910) compared to logistic regression (AUC 0.795, p < 0.001). The model also performed well for secondary outcomes: 30-day readmission (AUC 0.843, 95% CI: 0.779-0.899), 90-day readmission (AUC 0.848, 95% CI: 0.784-0.895), and 1-year mortality (AUC 0.873, 95% CI: 0.807-0.929), all significantly superior to logistic regression (all p < 0.001). At optimal thresholds, the model achieved sensitivity ranging from 62.71% to 90.24% and specificity from 67.84% to 87.85% across outcomes. SHAP analysis identified age (importance: 0.196), estimated glomerular filtration rate (0.181), medication count (0.159), serum albumin (0.147), and Charlson Comorbidity Index (0.138) as the most influential predictors. The model maintained good calibration (Brier scores: 0.156-0.164) and consistent performance across patient subgroups. SHAP threshold analysis identified eGFR < 45 mL/min/1.73 m² and serum albumin < 3.5 g/dL as key risk boundaries associated with markedly elevated adverse drug event risk. The XGBoost-SHAP model provides accurate, interpretable prediction of adverse outcomes in elderly cardiovascular patients with polypharmacy. This approach may facilitate personalized risk assessment and targeted interventions to improve medication safety in this vulnerable population.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 4","pages":"e70293"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369473","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":"Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence.","authors":"Petra Czarniak, Rachael Moorin, Jeff Hughes, Karl Gruber, David Youens","doi":"10.1002/prp2.70288","DOIUrl":"10.1002/prp2.70288","url":null,"abstract":"<p><p>The pregnane X receptor (PXR) gene encodes a ligand-activated protein involved with the metabolism and excretion of drugs, toxins, and other xenobiotics. The PXR protein is also an orphan nuclear receptor with a broad spectrum of potential ligands, including common prescription drugs, that can act as agonists or antagonists. Once activated, PXR upregulates several target genes involved in xenobiotic metabolism and can influence lipid and glucose metabolism, as well as the metabolism of commonly used drugs. In this review we searched the primary literature for articles reporting on drugs that regulate PXR and discuss potential clinical implications. Using the databases CINAHL, Embase, Medline, Scopus and Web of Science, we searched for terms related to PXR, following PRISMA guidelines. We screened 12 236 studies, 101 of which met the inclusion criteria, and included a further 46 research and review articles. We identified 42 studies reporting on prescription medications and 40 on non-prescription medications that regulate PXR as agonists or antagonists, and 47 studies reporting both beneficial and detrimental PXR-mediated effects of drugs on specific diseases, including different cancers, metabolic diseases, and inflammatory conditions, among others. We conclude that PXR is regulated by a broad range of drugs. Downstream effects of this regulation affect different diseases, leading to clinically relevant outcomes, such as altered efficacy of drugs or changes to the pathophysiology of a disease. Understanding and managing the agonist or antagonist role of drugs on PXR holds great potential to improve the health outcomes of different diseases. However, more information is needed about the potency of known PXR regulators.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 4","pages":"e70288"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437654","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 Pharmacology of the SLC15A4-TASL Complex, an Emerging Target for the Treatment of Lupus.","authors":"Alex L Wilkinson, Dillon Popat, Kathy Sengmany, Miguel C Silva, Steven J Charlton, Charles S Lay","doi":"10.1002/prp2.70295","DOIUrl":"10.1002/prp2.70295","url":null,"abstract":"<p><p>SLC15A4 is a member of the solute carrier superfamily that has been strongly linked to the pathogenesis of the auto-immune disease SLE. The endo-lysosomally localized SLC15A4 has traditionally been considered a proton-dependent histidine and peptide transporter, but has also been shown to facilitate TLR7, 8, and 9 induced IFN-alpha signaling in B cells and pDCs. New research has shown that SLC15A4 facilitates endo-lysosomal TLR signaling through a scaffolding interaction with a newly identified signal transducer, termed TASL. This interaction enables TLR7, 8, and 9 induced IRF5 activation, which is a crucial pathway in the pathogenesis of lupus. SLC15A4 is therefore an attractive target for the development of drugs for the treatment of SLE, and several small molecule SLC15A4 binders have now been reported which are capable of inhibiting TLR7, 8, or 9 signaling. This review summarizes the SLC15A4:TASL complex, its link to SLE, existing evidence for the transporter activity of SLC15A4, the current small molecule binders, and tools available for further drug discovery efforts.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 4","pages":"e70295"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448684","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":"3D Liver Fibrosis Models in Lab: A Novel Modality for Drug Screening.","authors":"Hani Keshavarz Alikhani, Fatemeh Majidi, Mahsa Ghasemzad, Anastasia Shpichka, Anastasia Nestorova, Zahra Hendi, Elham Rismani, Daria Kuznetsova, Peter Timashev, Massoud Vosough, Abbas Piryaei","doi":"10.1002/prp2.70306","DOIUrl":"10.1002/prp2.70306","url":null,"abstract":"<p><p>Liver fibrosis is the common consequence of liver injury caused by a variety of chronic liver disorders. This condition leads to the development of more severe complications, particularly cirrhosis and hepatocellular carcinoma. Despite abundant studies, the fundamental cell and molecular mechanisms of liver fibrosis are still unknown. There are many key players involved in the initiation and progression of liver fibrosis. Thus, the specific type of underlying disease and the study's objectives should be considered while choosing suitable models for liver fibrosis. Numerous in vitro and in vivo models have been generated to investigate liver fibrosis and proposed for drug screening and toxicology; however, there are no ideal in vitro models for drug discovery yet. In this review, we introduced the available in vitro models and highlighted certain platforms such as organoids and liver-on-a-chip for investigating liver fibrosis. Furthermore, we discussed the current challenges and potential application of each model.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 4","pages":"e70306"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648574","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}