Current drug targets最新文献

{"title":"Cytochrome P450 Enzymes in the Metabolism of Proton Pump Inhibitors: Implications for the Treatment of Peptic Ulcers.","authors":"Chetan Banbarilal Sharma, Shikha Yadav, Shatrudhan Prajapati","doi":"10.2174/0113894501451092260904093209","DOIUrl":"https://doi.org/10.2174/0113894501451092260904093209","url":null,"abstract":"<p><strong>Introduction: </strong>Peptic Ulcer Disease (PUD) remains a prevalent gastrointestinal condition primarily caused by Helicobacter pylori infection and chronic NSAID use. Proton Pump Inhibitors (PPIs) are the mainstay therapy, promoting mucosal healing through profound gastric acid suppression. However, variable clinical outcomes are frequently observed, largely influenced by individual differences in PPI metabolism mediated by cytochrome P450 (CYP450) enzymes, especially CYP2C19 and CYP3A4.</p><p><strong>Methods: </strong>The review is a critical analysis of the evidence on PPI pharmacokinetics, pharmacogenomics, and drug-drug interactions based on a structured search of PubMed, Scopus, and Web of Science, with predetermined inclusion and exclusion criteria to ensure equal consideration of studies on the topic.</p><p><strong>Results: </strong>Genetic polymorphisms in CYP2C19 create distinct metabolizer phenotypes-poor, intermediate, extensive, and ultrarapid-that markedly influence PPI plasma levels, intragastric pH control, and ulcer healing rates. Poor metabolizers exhibit superior healing due to prolonged acid suppression, while ultrarapid metabolizers are prone to treatment failure. Rabeprazole and ilaprazole, showing minimal CYP2C19 dependence, provide consistent efficacy across genotypes and reduced drug interaction potential.</p><p><strong>Discussion: </strong>Pharmacogenomic variability in CYP2C19 significantly affects therapeutic response and adverse outcomes. Personalized therapy based on genotype can optimize PPI efficacy, minimize toxicity, and reduce drug-drug interactions, particularly with agents such as clopidogrel.</p><p><strong>Conclusion: </strong>Incorporating CYP2C19 genotyping and pharmacogenomic data into clinical decisionmaking may improve treatment individualization, although evidence remains heterogeneous and context-dependent.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes in Ophthalmology: Bridging Physiological Barriers for Precision Ocular Drug Delivery.","authors":"Haranath Chinthaginjala, Bhargav E, A Thriveni, K Vamsi Vardhan, M Sai Kumar, Maddileti Repollu","doi":"10.2174/0113894501468995260904090347","DOIUrl":"https://doi.org/10.2174/0113894501468995260904090347","url":null,"abstract":"<p><strong>Introduction: </strong>Eye disorders such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis persist as prominent contributors to visual impairment on a global scale. Conventional ocular drug delivery systems face a range of physiological hurdles, including tear film clearance, epithelium absorption, conjunctival absorption, and the formidable blood-retinal barrier. These challenges culminate in suboptimal ocular bioavailability, frequently compelling healthcare providers to resort to invasive drug administration methods.</p><p><strong>Methods: </strong>This review systematically evaluates recent literature focusing on exosome-based ocular drug delivery systems. Published preclinical and clinical studies were identified through structured searches of PubMed, Scopus, and Web of Science using the keywords \"exosomes\", \"extracellular vesicles\", \"ocular drug delivery\", \"retina\", and \"ophthalmology\". The search covered studies published between 2000 and 2025 to understand exosome biology, isolation and characterization techniques, drug-loading strategies, and their ability to overcome ocular physiological barriers.</p><p><strong>Results: </strong>Exosomes are naturally occurring extracellular vesicles enriched with proteins, lipids, and nucleic acids, exhibiting excellent biocompatibility and intrinsic targeting capabilities. Evidence from preclinical studies demonstrates their ability to traverse ocular barriers and enhance drug retention and bioavailability. Emerging clinical investigations highlight their therapeutic promise in retinal and anterior segment disorders.</p><p><strong>Discussion: </strong>Compared with synthetic nanocarriers, exosomes offer superior biological stability, reduced immunogenicity, and enhanced tissue penetration. However, challenges related to largescale production, standardization, storage stability, immunological safety, and regulatory approval remain critical barriers to clinical translation.</p><p><strong>Conclusion: </strong>Exosome-based ocular drug delivery represents a promising precision medicine strategy that addresses long-standing limitations of conventional ophthalmic therapies. Continued advances in formulation optimization, scalable manufacturing, and regulatory frameworks are expected to accelerate their clinical and commercial translation for patient-centered eye care.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indomethacin as a Multi-target Anticancer Agent via Transmembrane Receptor-mediated Tumor Suppression: The Need for de novo Drug Derivatization.","authors":"Ebru Ozturk, Ghassan Issa, Soykan Ağar","doi":"10.2174/0113894501514656260908051336","DOIUrl":"https://doi.org/10.2174/0113894501514656260908051336","url":null,"abstract":"<p><strong>Introduction: </strong>Besides COX-inhibitory activities, other mechanisms underlying indomethacin's potential as an anticancer agent are being explored, including those related to the mediation of prostaglandin signaling through transmembrane receptors in solid tumors.</p><p><strong>Methods: </strong>In this mini-review, we summarize available information about modulation of transmembrane receptor signaling by indomethacin, including death receptors, EP receptors, receptor tyrosine kinases (RTKs), chemokine receptors, cannabinoid receptors, ACE2, P2X7, IP, and FZD/LRP5/6 receptors associated with Wnt pathways.</p><p><strong>Results: </strong>The presented data indicate that indomethacin may inhibit PGE₂-induced EP signaling, affect EGFR/FGFR and CXCR3 signaling pathways, increase death receptor-mediated apoptosis, and influence various types of receptor cross-talk involved in proliferation, angiogenesis, immune evasion, invasion, and metastasis. However, the most consistent results were obtained in colorectal cancer cells, while the role of indomethacin in breast, ovarian, and prostate cancers appears to be more contextual and receptor-profile dependent.</p><p><strong>Discussion: </strong>Overall, our review suggests that indomethacin functions mainly as a receptor signaling modulator rather than a selective receptor antagonist. The potential clinical application of indomethacin for cancer treatment is hindered by its poor selectivity towards COX enzymes, toxicity, and lack of specificity.</p><p><strong>Conclusion: </strong>Despite the possibility of using indomethacin as a template structure for creating more selective drugs, it seems that indomethacin cannot serve as a drug for anticancer therapy alone. This conclusion specifically positions parent indomethacin as a chemically modifiable scaffold for rational derivative development rather than as a final therapeutic endpoint.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinazoline-based VEGFR-2 Inhibitors: A Comprehensive Review of Design Strategies, SAR, and Therapeutic Advances.","authors":"Adarsh Kumar Yadav, Drashti Shah, Princy Desai, Utkarsha Kulkarni, Ashish Shah, Afzal Nagani, Paresh Patel, Divy Patel, Ashish Patel","doi":"10.2174/0113894501475706260831062144","DOIUrl":"https://doi.org/10.2174/0113894501475706260831062144","url":null,"abstract":"<p><strong>Introduction: </strong>Angiogenesis, primarily controlled by Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), significantly influences tumor growth and metastasis. Consequently, VEGFR-2 targeting has emerged as an important strategy for cancer treatment. Owing to their known efficacy as strong tyrosine kinase inhibitors, quinazoline-based heterocycles have attracted considerable interest in medicinal chemistry.</p><p><strong>Methods: </strong>The pharmacophoric properties, Structure-Activity Relationship (SAR) insights, and therapeutic advancements of quinazoline-based VEGFR-2 inhibitors documented in recent literature were thoroughly examined in this review.</p><p><strong>Results: </strong>By interacting with the DFG motif (Aspartate-Phenylalanine-Glycine) and forming hydrogen bonds with essential hinge residues like Cys919, Glu885, and Asp1046, quinazoline scaffolds effectively inhibit VEGFR-2. According to SAR studies, the quinazoline core is essential for increasing potency and selectivity when coupled with urea or amide bonds and electron-withdrawing substituents. Derivatives with better inhibitory activity have been produced through recent structural changes, such as halogen substitutions and fused heterocycles.</p><p><strong>Discussion and conclusion: </strong>Quinazolines serve as efficient scaffolds for occupying hydrophobic subpockets within the VEGFR-2 active site, as discussed. These results highlight the clinical importance of quinazoline derivatives and imply that the development of hybrid analogues in the future has enormous potential to advance targeted cancer treatments.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Brain: Are Nanodrugs Ready for Clinical Translation in CNS Disorders?","authors":"Ramandeep Saini, Mantosh Kumar Satapathy","doi":"10.2174/0113894501515112260901061515","DOIUrl":"https://doi.org/10.2174/0113894501515112260901061515","url":null,"abstract":"<p><p>Although significant progress has been made in nanotechnology, the clinical translation of central nervous system (CNS) therapeutics has been limited. While engineered nanocarriers have greatly enhanced blood-brain barrier (BBB) transport, there is now growing evidence that enhanced brain delivery is not sufficient for therapeutic success. Based on this, it is suggested that the key obstacle to translation is now the poor engagement of the molecule at the BBB, its intracellular pharmacology, and its pharmacodynamic response. This perspective underscores the evolving paradigm shift from delivery-based nanomedicine to target-based precision pharmacology where therapeutic engagement is quantified by target occupancy, pathway modulation in the context of disease, and translational relevance to the human condition. This integration of validated disease biology and intelligent delivery design can now be achieved through the advent of new technologies such as artificial intelligence (AI), systems pharmacology, receptor-guided engineering of nanocarriers, spatial multi-omics, brain organoids, and BBB-on-chip technologies. This target-oriented approach is expected to facilitate clinical reproducibility and accelerate the development of safer, more effective, and individualized nanotherapeutics for CNS diseases.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-1β-driven SERPINE1 Upregulation is Associated with CAD-ICM-related Cardiomyocyte Remodeling.","authors":"Kexin Chen, Xingyu He, Xiangming Ning, Yao Wang, Na Li, Teng Hu, Zeyuan Ma, Fengrui Yang, Yinlei Zhang, Jun Ma, Zheng Shi","doi":"10.2174/0113894501492572260831052957","DOIUrl":"https://doi.org/10.2174/0113894501492572260831052957","url":null,"abstract":"<p><strong>Introduction: </strong>Coronary artery disease (CAD) may progress to ischemic cardiomyopathy (ICM) and heart failure through maladaptive cardiomyocyte remodeling and myocardial fibrosis. This study aimed to identify key molecular mediators linking inflammatory and fibrotic signaling during this pathological transition.</p><p><strong>Methods: </strong>Single-cell RNA sequencing data from human ventricular tissues, including 2 CAD, 3 ICM, and 3 healthy samples (12,818 cells; 7 cell clusters), were integrated for analysis. Cell-cell communication and pseudotime trajectory analyses were performed. Findings were further validated using a bulk transcriptomic dataset (GSE57338), a left anterior descending artery ligation mouse model, and in vitro experiments in AC16 cardiomyocytes.</p><p><strong>Results: </strong>Cardiomyocyte trajectory analysis revealed a progressive upregulation of SERPINE1 from CAD to ICM, accompanied by an expansion of SERPINE1+ cardiomyocytes enriched in inflammation- related pathways. Bulk transcriptomic data and in vivo experiments confirmed increased SERPINE1 expression in diseased myocardium. In vitro, IL-1β stimulation increased SERPINE1 expression and secretion while reducing p-SMAD2 levels. Isoproterenol (ISO) stimulation concurrently did not significantly alter SERPINE1 and SMAD2/p-SMAD2. Cardiomyocyte-specific SERPINE1 knockdown in mice partially reversed ISO-induced upregulation of fibrotic/ECM genes (Postn, Col1a1, Col3a1, Acta2), confirming its functional role in vivo.</p><p><strong>Discussion: </strong>These findings indicate that SERPINE1 is associated with inflammatory signaling during disease progression and may be regulated through mechanisms that are not fully aligned with canonical TGF-β signaling.</p><p><strong>Conclusion: </strong>SERPINE1 is dynamically regulated during CAD-to-ICM progression and may serve as a marker of disease progression. Its dissociation from canonical TGF-β signaling suggests a potential role for inflammation-related mechanisms in its regulation and in fibrotic remodeling.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Angiogenesis in Drug Discovery: Current Status and Future Directions.","authors":"Sharon Blessy, Vijay R Chidrawar, Ashwini Deshpande","doi":"10.2174/0113894501483855260830110636","DOIUrl":"https://doi.org/10.2174/0113894501483855260830110636","url":null,"abstract":"<p><p>Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essential for development, tissue repair, and reproduction; however, dysregulation of angiogenesis contributes to cancer, ocular disorders, chronic inflammation, and cardiovascular diseases. Current antiangiogenic therapies that target VEGF/VEGFR signalling, tyrosine kinase pathways, or utilize monoclonal antibodies have improved clinical outcomes; however, their benefits remain limited by acquired resistance, transient efficacy, and treatment-associated toxicities. This review outlines the key molecular regulators of angiogenesis, including VEGF, FGF, PDGF, Ang/Tie, and HIF-mediated hypoxic signalling, and their interactions with the immune and stromal components of the microenvironment. It further summarizes the clinical landscape of approved antiangiogenic agents, highlighting gaps in response durability, lack of predictive biomarkers, and suboptimal patient selection. Emerging strategies, such as multi-target inhibitors, modulation of the tumour microenvironment, gene-based therapies, and advanced nanotechnology-enabled delivery systems, offer opportunities to enhance therapeutic precision and overcome resistance. Artificial intelligence-driven models integrating histology and multi-omics are reshaping personalized treatment selection and trial design. This review provides a roadmap for progressing from broad antiangiogenic therapy to mechanismdriven, biomarker-guided vascular medicine, while also considering pro-angiogenic approaches for regenerative applications.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-silico</i> Identification of Cyclic Peptide Inhibitors for A42r Profilin-like Protein from Monkeypox Virus.","authors":"Ahmad Firoz, Hani S H Mohammed Ali, Ihsan Ullah","doi":"10.2174/0113894501473387260824100136","DOIUrl":"https://doi.org/10.2174/0113894501473387260824100136","url":null,"abstract":"<p><strong>Introduction: </strong>The emergence of Monkeypox Virus (MPXV) as a major global health concern underscores an urgent unmet need for innovative antiviral therapeutics. To address this need, a novel large-scale in silico screening strategy was adopted to identify highly potent antiviral cyclic peptides that inhibit the A42R profilin-like protein of monkeypox virus.</p><p><strong>Methods: </strong>A total of 5,115 cyclic peptides were initially screened using Tanimoto similarity analysis, followed by data clustering to ensure structural diversity. From this, 500 representative peptides were selected and subjected to molecular docking against the A42R profilin-like protein. Subsequently, density functional theory calculations were performed to evaluate electronic properties. The topranked peptides were further analyzed using 300 ns molecular dynamics simulations conducted in triplicate to ensure reproducibility. Advanced analyses, including steered molecular dynamics, umbrella sampling, and MM/GBSA binding free energy calculations, were performed to assess the stability and binding affinity of the peptide-protein complexes.</p><p><strong>Results: </strong>Molecular docking identified 12 cyclic peptides with binding energies ≤ -6.0 kcal/mol (-6.5 to -6.1 kcal/mol), with CycPept_5184 showing the lowest score (-6.5 kcal/mol). Molecular dynamics simulations revealed that CycPept_3468 and CycPept_4348 maintained stable binding (RMSD of 1 nm), whereas CycPept_5184 and CycPept_5604 exhibited large fluctuations (up to 10 nm), indicating dissociation after 40 ns. MM/GBSA analysis confirmed favorable binding for both stable complexes, with CycPept_4348 showing a more negative binding free energy (-31.94 ± 5.01 kcal/mol) than CycPept_3468 (-26.09 ± 3.74 kcal/mol), driven primarily by stronger electrostatic interactions.</p><p><strong>Discussion: </strong>A multi-step computational screening strategy has been successfully used to narrow the large peptide library down to only two potent cyclic peptides. The combination of techniques in this simulation, including docking simulations, DFT methods, long-timescale MD simulations, and binding free energy calculations, improves the reliability of the predicted binding interactions.</p><p><strong>Conclusion: </strong>The objective of the present study was to identify cyclic peptides CycPept_3468 and CycPept_4348, which showed excellent inhibitory activity against the MPXV A42R profilin-like protein. The high binding affinity and structural stability of the peptides indicate their potential efficacy as antiviral drugs.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Druggable Protein Identification: Data-driven Multidimensional Representations and the Evolution of Predictive Models.","authors":"Hong-Qi Zhang, Hong-Ling Wang, Shang-Hua Liu, Yang Zhang, Rui-Qin Fang, Cui Luo, Jin-Song Su","doi":"10.2174/0113894501509808260821071728","DOIUrl":"https://doi.org/10.2174/0113894501509808260821071728","url":null,"abstract":"<p><p>Druggable proteins are proteins that can be specifically bound and modulated by drug molecules, with such modulation expected to produce therapeutic effects. The identification and validation of druggable proteins are central steps in modern drug discovery. With the rapid advancements in biological big data and artificial intelligence, computational methods based on bioinformatics have become essential for large-scale screening of druggable proteins. This review systematically summarizes the latest research progress in this field, providing a comprehensive analysis across three dimensions: data resources, feature engineering, and predictive models. The main contributions are 4-fold: First, we systematically describe three major types of databases: pharmacological annotation databases, quantitative affinity databases, and multi-source integrated databases, and dataset construction strategies as well as strategies for handling imbalanced samples are explored. Second, multi-level feature representations across four dimensions are categorized into sequencederived features, physicochemical properties, evolutionary information, and structural information, and the corresponding methods and tools are summarized. Third, we provide a detailed review of the evolution and application paradigms of predictive models, from classical machine learning and ensemble learning to deep learning architectures and protein large language models. Fourth, based on a systematic evaluation of representative studies, current limitations in areas such as few-shot learning and model interpretability are highlighted, and offer a forward-looking perspective on future research directions. This review aims to serve as a comprehensive reference for druggable protein prediction algorithms and to provide a solid theoretical and technical roadmap for computationally driven discovery of novel drug targets.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquiritigenin: Multifaceted Biological Activities and Mechanistic Insights.","authors":"Kaiyi Lai, Jiayu Zhang, Wenbo Gao, Yu Jiang, Ying Liu","doi":"10.2174/0113894501459655260817074939","DOIUrl":"https://doi.org/10.2174/0113894501459655260817074939","url":null,"abstract":"<p><strong>Introduction: </strong>Liquiritigenin (LQ), a bioactive flavonoid derived from licorice, exhibits a wide range of pharmacological activities. This review comprehensively summarizes the therapeutic potential of LQ and elucidates the molecular mechanisms underlying its principal effects, including hepatoprotective, anticancer, anti-inflammatory, cardioprotective, neuroprotective, and boneprotective activities.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, ResearchGate, and Web of Science. Studies investigating the therapeutic efficacy of LQ and related signaling pathways were selected for critical analysis.</p><p><strong>Results: </strong>LQ exerts diverse pharmacological effects through coordinated regulation of multiple signaling pathways. Its anti-inflammatory is primarily associated with suppression of NF-κB signaling and NLRP3 inflammasome, coupled with upregulation of the Nrf2-dependent antioxidant pathway. Anticancer effects involve suppression of tumor growth, metastasis, and survival through modulation of ER, ERK, PI3K/AKT/mTOR, HSP90, and glutamate receptor signaling pathways. Hepatoprotection is facilitated through PI3K/AKT-driven metabolic regulation and inhibition of TGF-β1/Smadmediated fibrotic processes. Neuroprotective effects are linked to ERβ activation, stimulation of the BDNF/ERK/CREB axis, and downregulation of PI3K/AKT/mTOR signaling. Cardioprotection involves attenuation of fibrosis, oxidative stress, and calcium overload. In the skeletal system, LQ promotes osteogenesis while inhibiting osteoclast activity. Additional protective effects have been documented in renal, testicular, cutaneous, and embryonic tissues through diverse signaling pathways.</p><p><strong>Discussion and conclusion: </strong>This review consolidates evidence for the multifaceted pharmacological activities of LQ and provides a mechanistic synthesis of its actions. These findings offer a valuable framework for future preclinical and translational investigations while highlighting important opportunities and challenges for further development.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}