Current drug targets最新文献

{"title":"Targets Involved in the Pharmacology of Bothrops Snakebite: <i>Statu Quo</i> and Future Perspectives.","authors":"Alisson Emannuel Franco Alves, Allessya Lara Dantas Formiga, Ana Flavia Chaves Uchoa, Anny Leticia Marinho Ramos Cardoso, Eduardo Oliveira Aquino Leal Rodrigues, Graziela Maria de Araujo Pereira, Julia de Padua Farias Bezerra Leite, Luis Fellipe Alves da Silva, Natalia Ferreira de Sousa, Marcelo da Silva Sobral, Marcus Tullius Scotti, Luciana Scotti, Francisco Humberto Xavier Junior","doi":"10.2174/0113894501352925250225045555","DOIUrl":"10.2174/0113894501352925250225045555","url":null,"abstract":"<p><p>Despite their hazardous nature, snake venoms hold immense potential for the development of novel therapies. This summary delves into the key aspects of snake venom research, focusing on their significance as targets for neutralization, their utility as novel drugs, the application of in silico studies, and future prospects with nanotechnology. Significance of Snake Venom: Snake venom harbors a rich diversity of toxic proteins with a wide range of biological activities. Its importance lies in the possibility of neutralizing its detrimental effects and exploring its therapeutic potential for diverse ailments. Venom Neutralization: The development of more effective and specific antivenoms is crucial for treating snakebites, particularly in regions with a high prevalence of accidents. Molecular-level venom studies are essential for identifying novel targets for the development of more efficacious antivenoms. Venom as a Source of Novel Drugs: Proteins present in snake venom exhibit diverse pharmacological activities, including antithrombotic, anti-inflammatory, analgesic, and antimicrobial properties. Investigating these proteins can lead to the development of novel medications for various diseases. In silico Studies: Bioinformatics tools and molecular modelling can aid in the discovery of novel molecular targets in snake venom, accelerating the process of developing new drugs and therapies. Nanotechnology for Drug Delivery: Nanotechnology offers new possibilities for developing more efficient and targeted drug delivery systems, enhancing the safety and effectiveness of snake venom- based treatments. Snake venom research represents a promising area of inquiry with immense potential for the development of novel drugs and therapies. The integration of traditional and innovative techniques, such as <i>in silico</i> studies and nanotechnology, can accelerate this process and contribute to the advancement of public health.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"454-469"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522840","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 Neurodegeneration: The Emerging Role of Hybrid Drugs.","authors":"Debasmita Deb, Meenakshi Dhanawat, Bharat Bhushan, Lalduhsanga Pachuau, Nirupam Das","doi":"10.2174/0113894501365588250131073304","DOIUrl":"10.2174/0113894501365588250131073304","url":null,"abstract":"<p><p>Neuron loss is the main feature of neurodegenerative diseases. The two most prevalent neurodegenerative illnesses are Parkinson's and Alzheimer's diseases. While several medications are currently approved to treat neurodegenerative disorders, most of them only address the symptoms that are related to the disorders. Owing to their severity and complex multifactorial pathophysiology, the approved medications currently in clinical use have not demonstrated sufficient efficacy and have limited therapeutic options. Enhancing medicine quality can be achieved using highly efficient conjugate chemistry methods, necessitating ongoing discovery efforts on hybrid drugs in academia and industry. The present review illustrates hybrid compounds and the design strategies that helped to create them. Developing multi-target directed ligands (MTDLs) is a more advantageous and sensible strategy for treating long-term complex illnesses like neurodegenerative diseases. Compared to classic treatments, hybrid drugs can deliver combination therapies in a single multifunctional agent, making them more potent and specific. Three main objectives are being initiated by using hybridization techniques in drug design: (i) increasing selectivity, (ii) improving activity, and (iii) reducing toxicity. The development of hybrid medications may offer a valuable method for producing compounds that are less likely to develop resistance and more likely to be effective. Hybrid drugs hold great promise, but a few technical and regulatory obstacles must be overcome before they can be successfully used in clinical settings.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"410-434"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364243","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":"From Structure to Function: Isatin Derivatives as a Promising Class of Antiviral Agents.","authors":"Anshul Jamwal, Shagun Sharma, Vijay Kumar Kapoor, Raveen Chauhan, Kamal Dua, Vikrant Dalwal, Akshay Kumar, Parteek Prasher, Poonam Negi","doi":"10.2174/0113894501352560250115054156","DOIUrl":"10.2174/0113894501352560250115054156","url":null,"abstract":"<p><p>A range of heterocyclic compounds, including Isatin (oneH-indole-2, 3-dione) and its by-products, have been shown to represent potential unit blocks in the synthesis of potential medicinal agents. Numerous studies have been carried out on isatin, its synthesis, biological uses, and its chemical composition since when it was discovered. Functionally, these isatin-containing heterocycles have demonstrated antibacterial, antidiabetic, antiviral, antitubercular, and anticancer properties, among many others. <i>In vitro</i> and <i>In vivo</i> efficaciousness of several Isatin moieties has been assessed in recent years based on their antimicrobial qualities. Isatin has shown great promise as a flexible heterocycle in the realm of drug development in recent years. Many viruses have caused extensive epidemics during the last 50 years, which have had detrimental effects on social, economic, and health conditions. The current unprecedented SARS-CoV-2 epidemic necessitates intensive research into the development of potent antiviral medications. It has been shown that Isatin, a flexible heterocycle, has a great deal of potential for drug development. Appropriately functionalized Isatin compounds have shown noteworthy and extensive antiviral activities throughout the last fifty years. The goal of this study is to gather all known data on Isatin derivatives' antiviral activity, emphasizing their structure-activity correlations as well as research on mechanistic and molecular modelling. We think that the scientific community will find this review to be a useful tool in the development of more efficient and powerful antiviral treatments based on Isatin scaffolds.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"470-488"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058281","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":"An Overview of Research Advances in Oncology Regarding the Transcription Factor ATF4.","authors":"Yulu Chen, Qi Gao, Dan Wang, Xun Zou, Xiuming Li, Jing Ji, Bin Liu","doi":"10.2174/0113894501328461240921062056","DOIUrl":"10.2174/0113894501328461240921062056","url":null,"abstract":"<p><p>This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"59-72"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343142","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":"Precision Targeting of BET Proteins - Navigating Disease Pathways, Inhibitor Insights, and Shaping Therapeutic Frontiers: A Comprehensive Review.","authors":"Rakesh D Amrutkar, Mehul V Amesar, Lokesh B Chavan, Nilesh S Baviskar, Vaibhav G Bhamare","doi":"10.2174/0113894501304747240823111337","DOIUrl":"10.2174/0113894501304747240823111337","url":null,"abstract":"<p><p>The family of proteins known as Bromodomain and Extra-Terminal (BET) proteins has become a key participant in the control of gene expression, having a significant impact on numerous physiological and pathological mechanisms. This review offers a thorough investigation of the BET protein family, clarifying its various roles in essential cellular processes and its connection to a variety of illnesses, from inflammatory disorders to cancer. The article explores the structural and functional features of BET proteins, emphasizing their special bromodomain modules that control chromatin dynamics by identifying acetylated histones. BET proteins' complex roles in the development of cardiovascular, neurodegenerative, and cancer diseases are carefully investigated, providing insight into possible treatment avenues. In addition, the review carefully examines the history and relevance of BET inhibitors, demonstrating their capacity to modify gene expression profiles and specifically target BET proteins. The encouraging outcomes of preclinical and clinical research highlight BET inhibitors' therapeutic potential across a range of disease contexts. The article summarizes the state of BET inhibitors today and makes predictions about the challenges and future directions of the field. This article provides insights into the changing field of BET protein-targeted interventions by discussing the potential of personalized medicine and combination therapies involving BET inhibitors. This thorough analysis combines many aspects of BET proteins, such as their physiological roles and their roles in pathophysiological conditions. As such, it is an invaluable tool for scientists and medical professionals who are trying to figure out how to treat patients by using this fascinating protein family.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"147-166"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388741","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 on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.","authors":"Chandrashekhar Sahu, Ram Kumar Sahu, Amit Roy","doi":"10.2174/0113894501312571240920070441","DOIUrl":"10.2174/0113894501312571240920070441","url":null,"abstract":"<p><p>The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"167-187"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388739","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":"Envisioning Glucose Transporters (GLUTs and SGLTs) as Novel Intervention against Cancer: Drug Discovery Perspective and Targeting Approach.","authors":"Sadat Shafi, Mohammad Ahmed Khan, Javed Ahmad, Syed Arman Rabbani, Shailja Singh, Abul Kalam Najmi","doi":"10.2174/0113894501335877240926101134","DOIUrl":"10.2174/0113894501335877240926101134","url":null,"abstract":"<p><p>Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"109-131"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388740","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":"LncRNA HAGLROS: A Vital Oncogenic Propellant in Various Human Cancers.","authors":"Jingjie Yang, Haodong He, Lihan Chen, Yuzhang Wei, Yulong Liu, Xiaolan Li, Chengfu Yuan","doi":"10.2174/0113894501345632241022055444","DOIUrl":"10.2174/0113894501345632241022055444","url":null,"abstract":"<p><p>HAGLR Opposite Strand lncRNA (HAGLROS) is a long non-coding RNA (lncRNA) located on the long arm of human chromosome 2 at locus 2q31.1. Emerging evidence highlights HAGLROS as a pivotal player in human cancers, characterized by its significant upregulation across multiple malignancies where it functions as an oncogenic driver. Its aberrant expression is closely linked to the initiation and progression of 13 distinct cancer types, notably correlating with adverse clinical outcomes and reduced overall survival rates in 9 of these cancer types. Mechanistically, HAGLROS is under the regulatory influence of the transcription factor STAT3, exerts competitive binding to 9 miRNAs, activates 5 signaling pathways pivotal for cancer cell proliferation and metastasis, as well as intricately modulates gene expression profiles. Given its multifaceted roles, HAGLROS emerges as a promising candidate for cancer diagnostics and prognostics. Moreover, its potential as a therapeutic target holds considerable promise for novel treatment strategies in oncology. This review synthesizes current research on HAGLROS, covering its expression patterns, biological roles, and clinical significance in cancer. By shedding light on these aspects, this review aims to contribute new perspectives that advance our understanding of cancer biology, enhance diagnostic accuracy, refine prognostic assessments, and pave the way for targeted therapeutic interventions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"267-281"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557348","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":"Proteases and Osteoporosis: A Comprehensive Review of Their Role in Bone Health.","authors":"Syed Sufian Ahmad, Faraha Ahmed, Sayeed Ahmad, Mohammad Ahmed Khan","doi":"10.2174/0113894501368814250212111828","DOIUrl":"10.2174/0113894501368814250212111828","url":null,"abstract":"<p><p>Proteases, once thought to degrade proteins solely, are also recognized as key signaling molecules central to numerous physiological processes, including bone remodeling. Dysregulated protease contributes to various pathological diseases, including cardiovascular diseases, cancer, inflammation, osteoporosis, and neurological disorders. Protease targeting is now quite far along; some small molecules are already on the market, and others are in development. Despite drugs having been successfully developed to inhibit well-defined proteases, including angiotensin-converting enzyme and HIV protease, designing selective inhibitors for the newly identified protease targets is still difficult owing to problems like poor target selectivity. This review covers principles guiding the discovery of protease drugs with focus on recent approaches, including the use of allosteric sites. In bone remodeling, proteases are involved in the regulation of cell surface properties and extracellular matrix in the degradation process that is fundamental to bone mineral density and quality. In particular, cathepsins, dipeptidyl peptidases, and caspases have become attractive targets for the therapy of osteoporosis. Selective inhibitors are different from other drugs in the way that they selectively inhibit bone resorption processes and do not bear on osteoblast survival factors or bone formation. However, some inhibitors proved to be effective in increasing bone density in osteoporotic patients, but due to side effects, they were withdrawn, highlighting the necessity of selective inhibitors. Newer generations of selective allosteric inhibitors aiming at protease activity would be safer and give an unexplored therapeutic angle to tackle osteoporosis without interfering with other physiological processes.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"489-505"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432449","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":"Current Updates on Pathogenesis, Systemic Therapy, and Treatment of Invasive Fungal Infections.","authors":"Sushil Kumar Singh, Shyam Sunder Pancholi","doi":"10.2174/0113894501337502241015121015","DOIUrl":"10.2174/0113894501337502241015121015","url":null,"abstract":"<p><p>Numerous health hazards are associated with fungal infections, ranging from asymptomatic cases to potentially fatal invasive diseases that are especially dangerous for those with impaired immune systems. The main causes behind these diseases are opportunistic fungi, namely <i>Aspergillus, Candida</i>, and <i>Cryptococcus</i>. Invasive fungal infections (IFIs) require a global response that includes the development of vaccines, standardized protocols for diagnosis, potent antifungal medications, and strategies to stop drug-resistant strains. Improving high-risk group diagnosis and treatment is essential to lowering death rates. This review highlights the substantial health concerns associated with fungal infections, especially in immunocompromised individuals, and identifies <i>Aspergillus, Candida</i>, and <i>Cryptococcus</i> as the main pathogens. It highlights the necessity of international efforts, such as the development of novel diagnostic instruments, imaging methods, and antifungal drugs, to combat these invasive infections. The review also addresses the increasing need for novel treatment approaches in light of the developing resistance to widely used antifungal medications. Furthermore, the significance of secretory proteins in fungal pathogenicity and the potential of combination therapy are investigated. It is also suggested that a multimodal strategy be used to fight these illnesses, given the promise of multivalent vaccinations. Overall, this study emphasizes how critical it is to develop better diagnostic and treatment strategies in order to successfully control and lessen the impact of invasive fungal diseases on the health of the world.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"203-220"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459972","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}