Current drug targets最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-08","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":"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 B Bhamare","doi":"10.2174/0113894501304747240823111337","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-08","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":"In Vivo Models of Steroid-Induced Intraocular Hypertension","authors":"Wanyu Tang, Yalong Dang","doi":"10.2174/0113894501333936240801053620","DOIUrl":"https://doi.org/10.2174/0113894501333936240801053620","url":null,"abstract":"Corticosteroids are widely utilized for their anti-inflammatory and immunosuppressive properties but often lead to ocular complications, including ocular hypertension. If untreated, ocular hypertension can progress to optic nerve atrophy and eventually result in steroid-induced glaucoma, which poses a risk of irreversible visual damage. Approximately 40% of individuals experience increased intraocular pressure after steroid use, and around 6% develop glaucoma. Although steroid-induced glaucoma is usually temporary and reversible if the treatment duration is under a year, prolonged exposure can cause permanent vision impairment. The pathogenesis of steroid-induced glaucoma is suggested to arise from increased outflow resistance of aqueous humor, primarily due to decreased expression of matrix metalloproteinases. This deficiency promotes the deposition of extracellular matrix and the dysfunction of trabecular meshwork cells. Additionally, modifications in the actin cytoskeleton increase the stiffness and alter the morphology of trabecular meshwork, further impeding aqueous humor outflow. Molecular changes, such as elevated expression of the MYOC gene, have also been implicated in restricting aqueous outflow. Various animal models, including rats, mice, primates, rabbits, cattle, sheep, cats, and dogs, have been developed to study steroid-induced glaucoma. These models exhibit pathological, pathophysiological, and molecular similarities to human disease, making them valuable for research. This review aims to summarize common animal models of steroid-induced ocular hypertension, discussing their advantages and limitations. The goal is to help researchers select appropriate models for future studies, thereby advancing the understanding of disease mechanisms and developing preventive strategies.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"189 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268327","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":"Joint Screening and Identification of Potential Targets of Nitazoxanide by Affinity Chromatography and Label-Free Techniques.","authors":"Menghan Zhu, Dongxia Qi, Dongliang Chen, Wenchong Ye, Xiaoyang Wang, Chunmei Wang, Wen Zhou, Bin Zhou, Juan Li, Keyu Zhang","doi":"10.2174/0113894501297697240805103744","DOIUrl":"https://doi.org/10.2174/0113894501297697240805103744","url":null,"abstract":"<p><strong>Background: </strong>Nitazoxanide not only exhibits a broad spectrum of activities against various pathogens infecting animals and humans but also induces cellular autophagy. Currently, the pattern of action and subcellular targets of nitazoxanide-induced cellular autophagy are still unclear.</p><p><strong>Methods: </strong>To identify potential targets of nitazoxanide in mammalian cells, we developed an af-finity chromatography system using tizoxanide, a deacetyl derivative of nitazoxanide, as a ligand. Affinity chromatography was performed using VERO cell extracts on tizoxanide-biotin, and the isolated binding proteins were identified by mass spectrometry. Candidate target proteins ob-tained using affinity chromatography were co-analysed with the drug affinity response target sta-bility method. Fluorescent probes obtained by coupling rhodamine B to nitazoxanide were used for intracellular localisation of the binding targets. Solvent-induced protein precipitation profiling and thermal proteome profiling were used to further validate the binding proteins.</p><p><strong>Results: </strong>The joint analysis of the drug affinity response target stability method and affinity chro-matography resulted in the screening of six possible candidate target proteins. Fluorescent probes localised the nitazoxanide-binding protein around the nuclear membrane. Molecular docking re-vealed that the binding proteins mainly formed hydrogen bonds with the nitro group of nitazoxa-nide. Solvent-induced protein precipitation profiling and thermal proteome profiling further vali-dated SEC61A, PSMD12, and PRKAG1 as potential target proteins of nitazoxanide.</p><p><strong>Conclusion: </strong>The data supports the idea that nitazoxanide is a multifunctional compound with multiple targets.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016607","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":"Trends on Nanomedicines as Novel therapeutics Approach in Targeting Nociceptors for Relieving Pain.","authors":"Trilochan Satapathy, Deepak Sahu, Himanshu Sahu, Ravindra Kumar Pandey, Shiv Shankar Shukla, Beena Gidwani","doi":"10.2174/0113894501315521240725065617","DOIUrl":"https://doi.org/10.2174/0113894501315521240725065617","url":null,"abstract":"<p><p>An important sensation that warns of potential harm to a specific area of the body is pain. The prevalence of pain-related conditions globally is a significant and growing public health issue. Chronic pain affects an estimated 1.5 billion people worldwide, with prevalence rates varying by region and demographic factors. Along with diabetes, cardiovascular disease, and cancer, pain is among the most frequent medical diseases. Opioid analgesics are the mainstay of current pain therapies, which are ineffective. Opioid addiction and its potentially fatal side effects necessitate novel treatment strategies. Nanotechnology offers potential advantages in pain management by enabling targeted drug delivery, which can enhance the efficacy and reduce the side effects of analgesic medications. Additionally, nanoparticles can be designed to release drugs in a controlled manner, improving pain relief duration and consistency. This approach also allows for the delivery of therapeutics across biological barriers, potentially enhancing treatment outcomes for chronic pain conditions. Nanomedicine enables sensitive and focused treatments with fewer side effects than existing clinical pain medicines; it is worth exploring as a potential solution to these problems. Furthermore, medication delivery systems that use nanomaterials are being used to treat pain. Whether it's the distribution of a single medication or a combination of therapies, this review seeks to summarise the ways in which drug delivery systems based on nanomaterials can be utilised to successfully treat and alleviate pain. For the purpose of writing this paper, we consulted several online libraries, including Pubmed, Science Direct, Pubmed Prime, and the Cochrane Library, to gather fresh and up-to-date material. This overview delves into the ins and outs of pain's pathophysiology, the present state of pain treatment, potential new pain treatment targets, and the various initiatives that have been launched and are still in the works to address pain with nanotechnology. Recent developments in nanomaterials-based scavenging, gene therapy for pain aetiology, and nanoparticle-based medicine delivery for side effect reduction are highlighted. Analgesics have been further covered in our discussion on FDA-approved pharmaceuticals and clinical advancements.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981937","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":"Recent Advances in the Development of Alpha-Glucosidase and Alpha-Amylase Inhibitors in Type 2 Diabetes Management: Insights from In silico to In vitro Studies.","authors":"Fariya Khan, Mohsin Vahid Khan, Ajay Kumar, Salman Akhtar","doi":"10.2174/0113894501313365240722100902","DOIUrl":"https://doi.org/10.2174/0113894501313365240722100902","url":null,"abstract":"<p><p>Diabetes is a metabolic disorder caused by high glucose levels, leading to serious threats such as diabetic neuropathy and cardiovascular diseases. One of the most reliable measures for controlling postprandial hyperglycemia is to reduce the glucose level by inhibiting enzymes in the digestive system, such as Alpha-Glucosidase and Alpha-Amylase. Here, we have investigated the use of inhibitors to inhibit carbohydrate metabolism in order to restrict glucose levels in diabetic patients. Acarbose, Voglibose, and Miglitol are three inhibitors approved by the FDA that efficiently inhibit these two enzymes and thereby minimising hyperglycemia but are al-so significantly helpful in reducing the risk of cardiovascular effects. We also provide insight into the other known inhibitors currently available in the market. The adverse effects associated with other inhibitors emphasise the demand for the latest in silico screening and in vitro validation in the development of potent inhibitors with greater efficacy and safety for the treatment of Type 2 diabetes. The recent findings suggest that Alpha-Glucosidase and Alpha-Amylase play a major role in carbohydrate metabolism and triggering the increase in glucose levels. This review pro-vides the latest scientific literature findings related to these two enzymes as well as the role of primary and secondary inhibitors as potential candidates. Moreover, this review elaborates the framework on the mechanism of action, different plant sources of extraction of these enzymes, as well as kinetic assay of inhibitors and their interaction that can be used in future prospects to de-velop potential leads to combat Type 2 diabetes.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916271","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":"Effect of Rotenone on the Neurodegeneration among Different Models","authors":"Iqra Subhan, Yasir Hasan Siddique","doi":"10.2174/0113894501281496231226070459","DOIUrl":"https://doi.org/10.2174/0113894501281496231226070459","url":null,"abstract":": Rotenone is a naturally occurring plant product used as an insecticide, pesticide and piscicide. It is lipophilic in nature and can cross the blood-brain barrier and induce the degeneration of neurons. It inhibits the mitochondrial respiratory chain complex I and stops the transfer of electrons. It induces ROS generation, which impairs mitochondrial activity. Rotenone is a toxic agent which causes the death of neurons. The present review describes the effect of rotenone on neurodegeneration with an emphasis on behavioral, pathological and neuropathological components carried out on various experimental models such as cell lines, Drosophila melanogaster, mice and rats.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"54 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831910","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":"Chitosan-Based Nanocarriers for Pulmonary and Intranasal Drug Delivery Systems: A Comprehensive Overview of their Applications","authors":"Wasan Alwahsh, Shariza Sahudin, Hatim Alkhatib, Mohammad F. Bostanudin, Mohammad Alwahsh","doi":"10.2174/0113894501301747240417103321","DOIUrl":"https://doi.org/10.2174/0113894501301747240417103321","url":null,"abstract":": The optimization of respiratory health is important, and one avenue for achieving this is through the application of both Pulmonary Drug Delivery System (PDDS) and Intranasal Delivery (IND). PDDS offers immediate delivery of medication to the respiratory system, providing advantages, such as sustained regional drug concentration, tunable drug release, extended duration of action, and enhanced patient compliance. IND, renowned for its non-invasive nature and swift onset of action, presents a promising path for advancement. Modern PDDS and IND utilize various polymers, among which Chitosan (CS) stands out. CS is a biocompatible and biodegradable polysaccharide with unique physicochemical properties, making it well-suited for medical and pharmaceutical applications. The multiple positively charged amino groups present in CS facilitate its interaction with negatively charged mucous membranes, allowing CS to adsorb easily onto the mucosal surface. In addition, CS-based nanocarriers have been an important topic of research. Polymeric Nanoparticles (NPs), liposomes, dendrimers, microspheres, nanoemulsions, Solid Lipid Nanoparticles (SLNs), carbon nanotubes, and modified effective targeting systems compete as important ways of increasing pulmonary drug delivery with chitosan. This review covers the latest findings on CS-based nanocarriers and their applications.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"28 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810099","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 Recent Advances in the Function and Mechanism of Caveolin-1 in Retinal Neovascularization","authors":"Rui Zhang, Yalong Dang","doi":"10.2174/0113894501310201240403065930","DOIUrl":"https://doi.org/10.2174/0113894501310201240403065930","url":null,"abstract":": Retinal neovascularization diseases have relatively high rates of evitable blindness. Abnormal retinal neovascularization is their main hallmark, which can damage the structure and function of the eye and lead to impaired vision. Caveolin-1 is a membrane protein that is expressed in many types of retinal cells and is involved in retinal neovascularization. This review presents a comprehensive analysis of global research on specific functions of caveolin-1 in retinal neovascularization. We believe that the mechanism of action of caveolin-1 might be related to the regulation of relevant signal pathways and looked ahead the application prospects of modulating caveolin- 1 in retinal neovascularization diseases.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"32 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591980","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":"Cisplatin-Based Combination Therapy for Enhanced Cancer Treatment","authors":"Qi Li, Siwei Chen, Xiao Wang, Jia Cai, Hongwu Huang, Shengsong Tang, Dongxiu He","doi":"10.2174/0113894501294182240401060343","DOIUrl":"https://doi.org/10.2174/0113894501294182240401060343","url":null,"abstract":":: Cisplatin, a primary chemotherapeutic drug, is of great value in the realm of tumor treatment. However, its clinical efficacy is strictly hindered by issues, such as drug resistance, relapse, poor prognosis, and toxicity to normal tissue. Cisplatin-based combination therapy has garnered increasing attention in both preclinical and clinical cancer research for its ability to overcome resistance, reduce toxicity, and enhance anticancer effects. This review examines three primary co-administration strategies of cisplatin-based drug combinations and their respective advantages and disadvantages. Additionally, seven types of combination therapies involving cisplatin are discussed, focusing on their main therapeutic effects, mechanisms in preclinical research, and clinical applications. This review also discusses future prospects and challenges, aiming to offer guidance for the development of optimal cisplatin-based combination therapy regimens for improved cancer treatment.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":"12 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592171","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}