Current drug targets最新文献

{"title":"Trends of Artificial Intelligence (AI) Use in Drug Targets, Discovery and Development: Current Status and Future Perspectives.","authors":"Manmayee Mohapatra, Chittaranjan Sahu, Snehamayee Mohapatra","doi":"10.2174/0113894501322734241008163304","DOIUrl":"10.2174/0113894501322734241008163304","url":null,"abstract":"<p><p>The applications of artificial intelligence (AI) in pharmaceutical sectors have advanced drug discovery and development methods. AI has been applied in virtual drug design, molecule synthesis, advanced research, various screening methods, and decision-making processes. In the fourth industrial revolution, when medical discoveries are happening swiftly, AI technology is essential to reduce the costs, effort, and time in the pharmaceutical industry. Further, it will aid \"genome-based medicine\" and \"drug discovery.\" AI may prepare proactive databases according to diseases, disorders, and appropriate usage of drugs which will facilitate the required data for the process of drug development. The application of AI has improved clinical trials on patient selection in a population, stratification, and sample assessment such as biomarkers, effectiveness measures, dosage selection, and trial length. Various studies suggest AI could be perform better compared to conventional techniques in drug discovery. The present review focused on the positive impact of AI in drug discovery and development processes in the pharmaceutical industry and beneficial usage in health sectors as well.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"221-242"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544237","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":"Emerging Role of NAT10 as ac4C Writer in Inflammatory Diseases: Mechanisms and Therapeutic Applications.","authors":"Wencheng Zhang, Weiping Lu, Min Wang, Di Yao, Jun Ma, Xiaoyan Hu, Mengyuan Tao","doi":"10.2174/0113894501346709241202110834","DOIUrl":"10.2174/0113894501346709241202110834","url":null,"abstract":"<p><p>The incidence of inflammatory diseases, including infections, autoimmune disorders, and tumors, is consistently increasing year by year, posing a significant and growing threat to human health on a global scale. Recent research has indicated that RNA acetylation modification, a specific type of post-transcriptional modification, may play a critical role in the pathogenesis of these diseases. Among the various mechanisms of RNA modification, N-acetyltransferase 10 (NAT10) has been identified as the sole cytidine acetyltransferase in eukaryotes. NAT10 is responsible for acetylating mRNA cytosine, which leads to the formation of N4-acetylcytidine (ac4C), a modification that subsequently influences mRNA stability and translation efficiency. Despite these insights, the specific roles and underlying mechanisms by which RNA acetylation contributes to the onset and progression of inflammatory diseases remain largely unclear. This review aimed to elucidate the alterations in NAT10 expression, the modifications it induces in target genes, and its overall contribution to the pathogenesis of various inflammatory conditions. It has been observed that NAT10 expression tends to increase in most inflammatory conditions, thereby affecting the expression and function of target genes through the formation of ac4C. Furthermore, inhibitors targeting NAT10 present promising therapeutic avenues for treating inflammatory diseases by selectively blocking NAT10 activity, thereby preventing the modification of target genes and suppressing immune cell activation and inflammatory responses. This potential for therapeutic intervention underscores the critical importance of further research on NAT10's role in inflammatory disease pathogenesis, as understanding these mechanisms could lead to significant advancements in treatment strategies, potentially transforming the therapeutic landscape for these conditions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"282-294"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779633","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":"Statin Therapy and C-reactive Protein in Patients with Kidney Disease: A Systematic Review and Meta-analysis of Randomized Clinical Trials.","authors":"Bahman Razi, Danyal Imani, Saeed Aslani, Zeljko Reiner, Amirhossein Sahebkar","doi":"10.2174/0113894501302428240909150925","DOIUrl":"10.2174/0113894501302428240909150925","url":null,"abstract":"<p><strong>Background: </strong>Increased levels of inflammation markers in patients with kidney disease, particularly chronic kidney disease (CKD) is an important risk factor. This study explored whether the effect of more potent statins on inflammation in CKD patients is dose-dependent, whether there is any difference between the hydrophilic and lipophilic statins concerning their effects on inflammation markers in patients with CKD, and whether the duration of treatment with statins has any effect on markers of inflammation in these patients.</p><p><strong>Methods: </strong>A systematic literature search of Scopus, PubMed, and ISI Web of Science databases from inception to August 2022 was performed. Eligible studies were stratified based on a target population, intervention duration, dosage and type of statins (high intensity statin and moderate/ low intensity), and solubility of statins. Publication bias was evaluated using Begg's regression asymmetry test for visual inspection of funnel plots. Non-linear effects of dosage of statins and treatment duration were also examined by fractional polynomial modeling.</p><p><strong>Results: </strong>Meta-analysis of 10 RCTs (12 studies) on 264 patients with kidney disease and 254 controls showed a significant hs-CRP lowering effect of the dose of statin. Both hydrophilic and lipophilic statins had significant hs-CRP lowering effects. Meta-analysis of 6 publications (7 studies) evaluating the impact of statins on CRP in 235 patients and 197 control subjects showed a significant negative association between treatment with statins group and CRP levels.</p><p><strong>Conclusion: </strong>Statin treatment decreases significantly the levels of CRP and hs-CRP in patients with kidney disease.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"132-145"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343145","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":"Emerging Therapeutic Targets in Rheumatoid Arthritis: Focusing on HIF-1α, Nrf2, STATs, and RORγt.","authors":"Pradyuman Prajapati, Pankaj Singh, Gaurav Doshi","doi":"10.2174/0113894501372670250408074908","DOIUrl":"10.2174/0113894501372670250408074908","url":null,"abstract":"<p><p>Rheumatoid arthritis is a chronic autoimmune condition marked by persistent inflammation and joint deterioration, affecting millions of people worldwide. The objective of many of the drugs being prescribed for treating RA patients is to reduce inflammation and halt the progression of the disease. Additionally, several of these therapeutic options have disadvantages, namely the potential for illness recurrence and unfavorable side effects with prolonged usage. Due to these inefficiencies, treating RA now requires an entirely novel approach. In recent times, there has been a shift in emphasis towards directly targeting transcription factors (TFs) due to their crucial involvement in the progression of RA, triggering essential pro-inflammatory adhesion molecules, enzymes, chemokines, and cytokines. Considering this, researchers are investigating synthetic and natural compounds as potential options to target essential TFs and associated signaling pathways. This review focuses on the potential natural compounds and synthetic drugs to target four significant TFs, namely, hypoxia-inducible factor 1α, nuclear factor erythroid 2-related factor 2, retinoic acid-related orphan receptor gamma t, and signal transducer and activator and transcription, highlighting their contributions to revolutionizing RA treatment, thus aiming for more effective and safer therapeutic options. This review also offers an overview of the current status of various natural compounds and synthetic drugs under consideration for targeting the signaling pathways that trigger the activation of TFs.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"507-533"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955491","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":"Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management.","authors":"Himani Gupta, Uma Bhandari","doi":"10.2174/0113894501314788241008115712","DOIUrl":"10.2174/0113894501314788241008115712","url":null,"abstract":"<p><p>Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin- aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"188-202"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459973","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":"The Role of Glycolipids and their Toxicity in the Context of Nanomaterials and Nanoparticles: A Review of the Literature.","authors":"Moyu Li, Wenjin Peng, Siwei Zhu, Xianyu Chen, Li Li, Xiaolan Li, Chengfu Yuan","doi":"10.2174/0113894501347158250305074908","DOIUrl":"10.2174/0113894501347158250305074908","url":null,"abstract":"<p><strong>Introduction: </strong>Diseases triggered by glucose and lipid metabolic disorders, such as hyperglycemia and hyperlipidemia, have become a global health threat. According to statistics, diabetic patients have exceeded 463 million worldwide, and the prevalence of hyperlipidemia is also continuously rising. These glycolipid metabolic diseases not only significantly increase the risk of complications such as cardiovascular disease, stroke, and kidney disease but also impose a huge economic burden on the global healthcare system. Despite the continuous emergence of treatment methods for glucose and lipid metabolic diseases with the advancement of research technology, existing therapies still face many challenges. In recent years, the rapid development of nanotechnology has injected new vitality into the medical field. As an emerging research field, nanomedicine has attracted much attention for its application prospects in the treatment of glycolipid metabolic diseases. Nanotechnology is expected to provide more precise and efficient solutions for the treatment of these diseases, thereby reducing global health and economic pressures.</p><p><strong>Objective: </strong>The objective of this article is to comprehensively review the relationship between nanotechnology and glucose and lipid metabolism.</p><p><strong>Methods: </strong>We have carried out a series of literature searches, focusing on glycolipid effects and toxicity of nano-materials.</p><p><strong>Results: </strong>Nanoparticles as drug carriers or nanoparticles enhance bioavailability and activity. Nano-material-based optical reporters aid in detecting lysosome lipid content, facilitating treatment and drug development for glucose and lipid metabolism disorders. Additionally, nanomaterials find applications in glucose biofuel cells and microalgal lipid metabolism regulation. However, nanomaterials, such as polystyrene nanoplastics, may have toxic effects, inducing macrophage transformation and lipid accumulation in the liver.</p><p><strong>Conclusion: </strong>The development of nanotechnology is still in its infancy, and many disease-based studies are still in the stage of animal experiments and have not yet been applied in clinical practice. However, the universality and multilateralism of the use of nanotechnology give it excellent development prospects and also provide a research direction for medical research.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"571-585"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604045","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":"Emerging Combinatorial Drug Delivery Strategies for Breast Cancer: A Comprehensive Review.","authors":"Harshita Singhai, Sarjana Raikwar, Sunny Rathee, Sanjay K Jain","doi":"10.2174/0113894501352081241211090911","DOIUrl":"10.2174/0113894501352081241211090911","url":null,"abstract":"<p><p>Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action. Increasingly, the use of phytoconstituents alongside chemotherapeutic agents has shown promise in enhancing treatment outcomes. This combination therapy acts on key signaling pathways such as Hedgehog, Notch, Wnt/β- catenin, tyrosine kinases, and phosphatidylinositol 3-kinase (PI3K), which play critical roles in cellular proliferation, apoptosis, angiogenesis, differentiation, invasion, and metastasis. This review explores various signaling pathways involved in breast cancer progression, discusses conventional treatment methods like surgery, adjuvant radiotherapy, hormonal therapy, and chemotherapy, and highlights emerging nanocarrier-based drug delivery systems (DDS). Liposomes, dendrimers, exosomes, polymeric micelles, and nanoparticles (organic, inorganic, gold, magnetic, carbon-based, and quantum dots) are examined as innovative strategies for enhancing drug delivery efficacy. Furthermore, stimuli-responsive DDSs, including reactive oxygen species (ROS), enzyme-, and hypoxia- responsive systems, are presented as cutting-edge approaches to overcoming drug resistance. Special emphasis is placed on the co-delivery of chemotherapeutic agents and plant-based compounds, particularly in estrogen receptor-positive (ER+) breast cancer. This review aims to provide a comprehensive overview of novel combinatorial strategies and advanced nanocarriers for the effective and targeted treatment of breast cancer.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"331-349"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945591","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":"Advances in Cysteine Protease B Inhibitors for Leishmaniasis Treatment.","authors":"Ana Luisa Rodriguez Gini, Emilio Emilio João, Juliana Romano Lopes, Pamela Souza Tada Da Cunha, Angela Maria Arenas Velasquez, Marcia Aparecida Silva Graminha, Jean Leandro Dos Santos, Caue Benito Scarim","doi":"10.2174/0113894501324437240919064715","DOIUrl":"10.2174/0113894501324437240919064715","url":null,"abstract":"<p><p>The expression and release of cysteine proteases by <i>Leishmania</i> spp. and their virulence factors significantly influence the modulation of host immune responses and metabolism, rendering cysteine proteases intriguing targets for drug development. This review article explores the substantial role of cysteine protease B (CPB) in medicinal chemistry from 2001 to 2024, particularly concerning combatting <i>Leishmania</i> parasites. We delve into contemporary advancements and potential prospects associated with targeting cysteine proteases for therapeutic interventions against leishmaniasis, emphasizing drug discovery in this context. Computational analysis using the pkCSM tool assessed the physicochemical properties of compounds, providing valuable insights into their molecular characteristics and drug-like potential, enriching our understanding of the pharmacological profiles, and aiding rational inhibitor design. Our investigation highlights that while nonpeptidic compounds constitute the majority (69.2%, 36 compounds) of the dataset, peptidomimetic- based derivatives (30.8%, 16 compounds) also hold promise in medicinal chemistry. Evaluating the most promising compounds based on dissociation constant (<i>Ki</i>) and half maximal inhibitory concentration (IC₅₀) values revealed notable potency, with 41.7% and 80.0% of nonpeptidic compounds exhibiting values < 1 μM, respectively. On the other hand, all peptidic compounds evaluated for <i>Ki</i> (43.8%) and IC₅₀ (31.3%) obtained values < 1 μM, respectively. Further analysis identified specific compounds within both categories (nonpeptidic: 1, 2, and 4; peptidic: 48-52) as particularly promising, warranting deeper investigation into their structure-activity relationships. These findings underscore the diverse landscape of inhibitors in medicinal chemistry and highlight the potential of both nonpeptidic and peptide-based compounds as valuable assets in therapeutic development against leishmaniasis.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"88-108"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343140","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":"Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.","authors":"Maneesh Mohan, Ashi Mannan, Chirag Kakkar, Thakur Gurjeet Singh","doi":"10.2174/0113894501320839240918110656","DOIUrl":"10.2174/0113894501320839240918110656","url":null,"abstract":"<p><p>Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"33-58"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343144","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":"Emerging Threats and Challenges of Monkeypox Virus: Exploration and Sensitivity.","authors":"Sejal Porwal, Rishabha Malviya, Sathvik Belagodu Sridhar, Manjeet Kaur","doi":"10.2174/0113894501355177241107062738","DOIUrl":"10.2174/0113894501355177241107062738","url":null,"abstract":"","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"295-297"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926854","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}