Current drug targets最新文献

{"title":"Targeting the Toll-like Receptor Signaling Pathway in Lung Cancer: Therapeutic Opportunities and Challenges.","authors":"Muhammad Usama, Badar Raza, Mingfei Wu, Shanming Ji","doi":"10.2174/0113894501414090250903070446","DOIUrl":"https://doi.org/10.2174/0113894501414090250903070446","url":null,"abstract":"<p><p>Lung cancer, particularly non-small cell lung cancer, is a leading cause of global mortality, with many cases diagnosed at advanced stages. The Toll-Like Receptor (TLR) signaling pathway plays a crucial role in linking inflammation to lung cancer progression, with both pro-tumor and anti-tumor effects. This perspective delves into the complex functions of TLR proteins in lung cancers, elucidating their involvement in tumor growth, angiogenesis, and metastasis. In addition, we highlight the therapeutic potentials of TLR agonists and antagonists, emphasizing their interplay with immune checkpoint inhibitors like PD-1/PD-L1 blockers to overcome immunosuppressive barriers. Nevertheless, the paradoxical effects of TLR activation, balancing immune stimulation and suppression, demand precise targeting strategies. Collectively, our study synthesizes the current understanding of TLR signaling pathways in lung cancers, offering insights into their potential for advancing lung cancer therapies.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014061","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":"Sepsis-Associated Brain Dysfunction: Mechanisms, Clinical Insights, and Therapeutic Strategies.","authors":"Nazrana Payal, Juhi Saxena, Vijay Kumar Srivatsava, Sanket Kaushik, Arif Jamal Siddiqui, Kartik Chauhan, Aditi Sharma, Anupam Jyoti, Lalit Sharma","doi":"10.2174/0113894501381183250825144834","DOIUrl":"https://doi.org/10.2174/0113894501381183250825144834","url":null,"abstract":"<p><p>Sepsis is a lethal clinical condition representing severe inflammation and immune suppression to pathogen or infection, leading to tissue damage or organ dysfunction. Hyper-inflammation and immune suppression cause a fatal, escalated Blood-Brain Barrier permeability, being a secondary response towards infection resulting in sepsis-associated brain dysfunction. These changes in the BBB lead to the brain's susceptibility to increased morbidity and mortality. An important mechanism of sepsis-associated brain dysfunction includes excessive activation of microglial cells, altered brain endothelial barrier function, and BBB dysfunction. Lipopolysaccharide, a bacterial cell wall component (endotoxin), by forming a complex through membrane- bound CD receptors on macrophages, monocytes, and neutrophils, begins synthesizing anti- inflammatory agents for defense of the host, including nitric oxide, cytokines, chemokines, interleukins, and the complement system. Unrestrained endotoxemia and pro-inflammatory cytokines result in microglial as well as brain endothelial cell stimulation, downregulation of tight junctions, along with intense recruitment of leucocytes. Subsequent neuroinflammation, together with BBB dysfunction, aggravates brain pathology as well as worsens sepsis-associated brain dysfunction. The clinical demonstration includes mild (confusion and delirium) along with severe (cognitive impairment, coma, as well as sequel death). Different clinical neurophysiological evaluation parameters can be used for the quantification and important issues of the disorder, including SOFA, imaging methods, and the use of biomarkers associated with brain dysfunction. The present review addresses the mechanism, clinical examination, the long-term cognitive effects, and current treatment modalities for sepsis-associated brain dysfunction.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999805","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":"A Review of Amylin Peptide Receptor Activators for Obesity Pharmacotherapy.","authors":"Sangmin Lee","doi":"10.2174/0113894501398624250819070004","DOIUrl":"https://doi.org/10.2174/0113894501398624250819070004","url":null,"abstract":"<p><p>Amylin is a thirty-seven amino acid peptide hormone that is secreted from the pancreas with insulin. The peptide hormone amylin activates its receptors in the brain to regulate blood glucose and food appetite. Interestingly, the amylin receptor is the heterodimer of the calcitonin receptor (which is the receptor for the peptide hormone calcitonin) and an accessory protein called receptor activity-modifying protein. Amylin receptor activation has emerged as a promising drug target for the treatment of diabetes and obesity. Recent pharmaceutical efforts with amylin receptor activators have focused on developing drugs for the treatment of obesity. Multiple amylin analogs have been tested in pre-clinical settings, and some are currently being tested in clinical trials. In this review, recent research publications and available information regarding drug development targeting amylin receptors were searched. It summarizes the amylin receptor activators currently being tested in clinical trials for the treatment of obesity. In addition, recent research achievements were demonstrated, such as the introduction of mutations that enhanced receptor affinity/potency and the development of a method for measuring selective amylin receptor activation. Potential issues along with peptide drug development were described, including lipidation to achieve a long-acting property. The combination of an amylin analog and other anti-obesity peptide drugs has demonstrated higher clinical efficacy in reducing body weight than monotherapy. The combination therapy is likely to be the first drug therapy where an amylin analog is used for obesity treatment. In addition, amylin receptor activators may have an adverse effect profile more favorable than that of GLP-1 receptor activators, which could be a potential benefit of amylin receptor activators.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999854","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":"Betaine, a Potential Therapeutic Alternative for the Treatment of Depression.","authors":"Yue-Yue Zhang, Yuan-Yuan Cheng, Wei Guan","doi":"10.2174/0113894501394957250818110931","DOIUrl":"https://doi.org/10.2174/0113894501394957250818110931","url":null,"abstract":"<p><p>Depression is a debilitating psychiatric disorder characterized by loss of interest, anhedonia, and social isolation, which is projected to become the leading cause of disability worldwide by 2030. Despite the greater economic and social burden imposed by depression, the precise pathophysiology underlying the development of depression remains elusive. Betaine (N, N, N-trimethylglycine), an amino acid derivative, is widely distributed in various animals and plants and has been shown to have numerous beneficial effects, including antioxidant activities, anti-inflammatory functions, regulation of energy metabolism, and reduction of endoplasmic reticulum stress. It has been used to treat Alcohol-Associated Liver Disease (AALD), type 2 diabetes, cancer, obesity, and Alzheimer's Disease (AD). Interestingly, accumulating evidence has shown that betaine exerts a significant role in alleviating depressive-like behavior in patients and animals resulting from chronic stress. Although the antidepressant effects of betaine have not been compared with traditional antidepressants with insufficient verification, based on the neurobiological mechanisms of depression, it may be a potential alternative medicine for the treatment of depression. This is the first review aiming to provide a comprehensive overview of the remarkable effects of betaine in the pathophysiology of depression. These pieces of evidence are of great importance for deepening our understanding of the antidepressant mechanism of betaine, so as to develop betaine supplements for the supplementary treatment of depression.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999861","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":"Development of Novel Intravesical Formulation for Bladder Retention Targeting Bladder Disorders.","authors":"Varsha Harle, Yogeeta O Agrawal","doi":"10.2174/0113894501384020250804093144","DOIUrl":"https://doi.org/10.2174/0113894501384020250804093144","url":null,"abstract":"<p><p>Numerous bladder-related diseases, including urinary blockages, interstitial cystitis, overactive bladder syndrome, cancer, and infections of the urinary tract, can affect bladder function. The human urinary bladder's distinct anatomy successfully prevents any hazardous material from entering circulation. The pathogenesis was assessed according to the extent of invasion in the bladder wall tissue obtained through Transurethral Resection of Bladder Tumor (TURBT) and classified as Muscle-Invasive and Non-Muscle Invasive Bladder Cancer (MBIC and NMIBC). Intravesical Drug Delivery (IDD) has recently gained attention for treating bladder disorders. IDD refers to the insertion of a drug directly into the bladder using a catheter. Intravesical administration of immunotherapy or chemotherapy has been demonstrated to reduce recurrence rates and inhibit disease progression. In addition, several other systems, including recombinant BCG, gene therapy, vectors, and Antibody-Drug Conjugates (ADCs), are now used. Moreover, the novel intravesical formulations of distinct chemotherapeutic agents, including gemcitabine, Doxorubicin (DOX), and Mitomycin C (MMC), are used in bladder-related problems. Novel intravesical drugs, polymeric hydrogels, dendrimers, hydrogels, mucoadhesives, nanocarriers, and intravesical devices have been discussed. Aside from chemotherapy and immunotherapy, devices such as Gem- RIS, device-assisted hyperthermic intravesical chemotherapy, and photodynamic therapy are utilized.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798454","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":"Gut-Brain Dialogues in Fruit Fly (Drosophila melanogaster): How Peptide Hormones Bridge Metabolism, Longevity, and Behavioral Adaptation.","authors":"Mengzhe Tian, Shushen Sun, Qinghao Meng, Jingyi Li, Xinyi Li, Suxia Ren, Zengyi Huang, Shaoshan Du, Yiwen Wang","doi":"10.2174/0113894501397622250801062050","DOIUrl":"https://doi.org/10.2174/0113894501397622250801062050","url":null,"abstract":"<p><strong>Background: </strong>Gut-peptide hormones are crucial regulators of various physiological processes, including metabolism, digestion, behavior, and homeostasis. In Drosophila melanogaster, a widely used model organism, a diverse range of gut-peptide hormones governs gut-brain communication, influencing food intake, energy balance, circadian rhythms, stress responses, and aging.</p><p><strong>Objective: </strong>This review summarizes recent studies on gut-peptide hormones in D. melanogaster, focusing on their mechanisms of action, interactions with other signaling pathways, and their relevance to human orthologs.</p><p><strong>Methods: </strong>The PubMed database was searched for studies on gut-peptide hormones in D. melanogaster published in the past decade.</p><p><strong>Results: </strong>The functions of D. melanogaster gut-peptide hormones were reviewed, including DH31, Bursicon (Burs), Tachykinins (Tks), Hedgehog (Hh), Pigment-dispersing factor (PDF), Neuropeptide F (NPF), Short neuropeptide F (sNPF), Allatostatins (ASTs), CCHamides (CCHa), and Limostatin (Lst). These hormones regulate key physiological processes such as digestion, energy homeostasis, and metabolism through conserved pathways.</p><p><strong>Conclusion: </strong>Drosophila melanogaster gut-peptide hormones are fundamental regulators of health and disease. They are conducive to exploring conserved mechanisms for developing treatments against human metabolic and aging disorders.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798455","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":"Role of Artificial Intelligence in Nanomedicine and Organ-specific Therapy: An Updated Review.","authors":"Kuldeep Rajpoot","doi":"10.2174/0113894501394785250715165404","DOIUrl":"https://doi.org/10.2174/0113894501394785250715165404","url":null,"abstract":"<p><strong>Background: </strong>In organ-specific therapy, artificial intelligence (AI) is primarily used to improve surgical planning through image analysis, predict post-transplant outcomes, personalize treatment plans based on patient data, optimize organ allocation logistics, and donor-recipient precision mapping for organs to improve transplants. Furthermore, all these applications ultimately lead to better patient outcomes and enhanced organ therapy.</p><p><strong>Objective: </strong>This review aims to examine the revolutionary effects of AI in some key healthcare fields, such as nanomedicine, cancer treatment, clinical applications, and organ-specific delivery.</p><p><strong>Methods: </strong>This review article discusses in detail the role of AI in nanomedicine, cancer therapy, clinical applications, organ-specific delivery (e.g., cardiovascular, gastroenterology, kidney, liver, lung, ophthalmology, skin, etc.), diagnosis, and radiotherapy. In addition, it also discusses limitations and challenges of AI in healthcare.</p><p><strong>Results: </strong>AI-based clinical translation has potential but faces challenges like artifact vulnerability, ethical and legal considerations, and security measures. Restrictive data-use policies may hinder accurate analysis. Regulations and collaboration with data-sharing mechanisms could overcome barriers.</p><p><strong>Conclusion: </strong>AI is being utilized in organ-specific therapy to enhance donor-recipient matching, surgical planning, post-transplant outcomes prediction, and personalized treatment plans by analyzing patient data.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689167","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":"Innovative Strategies and Advances in Drug Delivery Systems to Address Poor Solubility: A Comprehensive Review.","authors":"Hossamaldeen Bakrey, Abdulkadir Abdu, Riya Shivgotra, Bindu Soni, Manya Sharma, Alaa Bakrey, Subheet Kumar Jain","doi":"10.2174/0113894501375776250713110838","DOIUrl":"https://doi.org/10.2174/0113894501375776250713110838","url":null,"abstract":"<p><p>Poor solubility remains a significant obstacle in drug administration, adversely affecting the bioavailability and therapeutic efficacy of many drugs. It is also recognized as a primary factor contributing to issues with bioavailability, such as poor, inconsistent, limited, and highly variable bioavailability of marketed products. It is estimated that 40% of marketed drugs face bioavailability challenges primarily due to poor water solubility, and about 90% of pharmacological compounds exhibit poor water solubility in their early development stages. Addressing this issue is crucial for improving drug performance, efficacy, and patient outcomes. This review provides an overview of the challenges associated with poorly soluble drugs, including low bioavailability, limited dissolution rates, inconsistent absorption, decreased patient compliance, formulation difficulties, and associated costs and time constraints. Numerous strategies have been now investigated to tackle the issue of poor solubility. This review offers an updated overview of commonly used macro and nano drug delivery systems, including micelles, nanoemulsions, dendrimers, liposomes, lipid-based delivery systems, microemulsions, cosolvents, polymeric micelle preparation, drug nanocrystals, solid dispersion methods, crystal engineering techniques, and microneedle- based systems. Additionally, the review examines advanced techniques like cyclodextrin- based delivery systems, co-solvency and co-crystallization approaches, polymeric micelles, spray drying, co-precipitation, and amorphous solid dispersion. The role of computational modeling and formulation prediction is also addressed. Recent advancements in protein-based approaches, 3D printing, mesoporous silica nanoparticles, supramolecular delivery systems, magnetic nanoparticles, nanostructured lipid carriers, and lipid-based nanoparticles are highlighted as novel solutions for enhancing the solubility of poorly soluble drugs. The review concludes with predictions for the future, emphasizing the potential for further innovation in drug delivery methods to overcome the challenges associated with poorly soluble drugs.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689165","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":"Modern Solutions to UTIs: The Role of Nanotechnology and Herbal Treatments.","authors":"Ashutosh Kumar, Amit Kumar, Md Moidul Islam, Ranadeep Borgohain, Sarjana Raikwar","doi":"10.2174/0113894501371882250713174322","DOIUrl":"https://doi.org/10.2174/0113894501371882250713174322","url":null,"abstract":"<p><strong>Introduction: </strong>Urinary tract infections (UTIs) range from mild to severe cases, commonly caused by uropathogenic Escherichia coli (E. coli). The growing concern about antibiotic resistance demands alternative treatment strategies. Nanotechnology, particularly nanocarriers, presents a promising solution by enhancing drug delivery, antibacterial activity, and targeted therapy. This review focuses on the emerging role of combining herbal remedies with nanotechnology for more effective and personalized management of UTIs, aiming to overcome the limitations of conventional antibiotic therapies.</p><p><strong>Methods: </strong>The review involved an extensive search of scientific databases and relevant literature, including studies published to date from PubMed, Science Direct, and Google Scholar. Urinary tract infections (UTI), antibiotic resistance, nanotechnology, drug delivery, targeted drug delivery, and herbal drugs were among the search phrases used.</p><p><strong>Result: </strong>According to studies, combining herbal extracts such as neem and turmeric with nanotechnology significantly enhances antimicrobial activity against UTI pathogens. These nanoformulations show enhanced bacterial inhibition, reduced inflammation, and increased therapeutic precision with minimal side effects.</p><p><strong>Discussion: </strong>The synergistic use of herbal remedies and nanocarriers offers a novel approach to managing UTIs. Nanotechnology not only enhances drug delivery but also improves diagnostic accuracy through fluorescence markers and biomolecule tagging. This strategy effectively addresses growing antibiotic resistance and supports the development of personalized treatments. The combination of natural bioactives and advanced delivery systems offers a safer, more effective alternative to conventional antibiotics in treating UTIs.</p><p><strong>Conclusion: </strong>The integration of nanotechnology and herbal therapies revolutionizes UTI management through precision medicine. This approach enhances treatment efficacy, diagnostic accuracy, and patient outcomes, offering a personalized solution to combat antibiotic resistance and urinary tract abnormalities with improved targeting and minimal side effects.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689166","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":"Therapeutic Drug Monitoring: A New Hope for Individualised Treatment with Venetoclax.","authors":"Yue Tang, Shuojiao Li, Peng Rao, Wenxian Yu, Xuanpeng Jiang, Jiatao Liu","doi":"10.2174/0113894501376271250710221018","DOIUrl":"https://doi.org/10.2174/0113894501376271250710221018","url":null,"abstract":"<p><p>B-cell lymphoma-2 (BCL-2) plays a key role in regulating apoptosis. Venetoclax (VEN), a BCL-2 inhibitor, has been approved for the treatment of a variety of haematologic malignancies. VEN is primarily metabolized by CYP3A, and a variety of factors (such as CYP3A inhibitors, as well as food and hepatic functions) have been reported to significantly influence the metabolic process. There is significant interindividual variability in VEN plasma concentrations, and studies have shown that its exposure levels are correlated with efficacy, although the relationship with adverse effects remains controversial. The value of applying of therapeutic drug monitoring (TDM) in individualized VEN therapy has been confirmed by some studies, but the optimal therapeutic window for different malignancies is still unclear. This review summarizes the pharmacokinetic characteristics, along with the factors influencing VEN pharmacokinetics, drug-drug interactions, and advancements in TDM research on VEN, aiming to provide a theoretical basis for TDM-guided individualized therapy.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658639","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}