Current drug targets最新文献

{"title":"Polypharmacology-Driven Discovery and Design of Highly Selective, Dual and Multitargeting Inhibitors of <i>Mycobacterium tuberculosis</i> - A Review.","authors":"Franklin V Amandy, Gabriel L L Neri, Joe A H Manzano, Adrian D Go, Allan P G Macabeo","doi":"10.2174/0113894501306302240526160804","DOIUrl":"10.2174/0113894501306302240526160804","url":null,"abstract":"<p><p>The increasing demand for novel antitubercular agents has been the main 'force' of many TB research efforts due to the uncontrolled growing number of drug-resistant strains of <i>M. tuberculosis</i> in the clinical setting. Many strategies have been employed to address the drug-resistant issue, including a trend that is gaining attention, which is the design and discovery of <i>Mtb</i> inhibitors that are either dual- or multitargeting. The multiple-target design concept is not new in medicinal chemistry. With a growing number of newly discovered <i>Mtb</i> proteins, numerous targets are now available for developing new biochemical/cell-based assays and computer-aided drug design (CADD) protocols. To describe the achievements and overarching picture of this field in anti- infective drug discovery, we provide in this review small molecules that exhibit profound inhibitory activity against the tubercle bacilli and are identified to trace two or more <i>Mtb</i> targets. This review also presents emerging design methodologies for developing new anti-TB agents, particularly tailored to structure-based CADD.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"620-634"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300277","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 Biomedical Applications of Mannans and Xylans.","authors":"Shriya Teli, Kajal Deshmukh, Tabassum Khan, Vasanti Suvarna","doi":"10.2174/0113894501285058240203094846","DOIUrl":"10.2174/0113894501285058240203094846","url":null,"abstract":"<p><p>Plant-based phytochemicals, including flavonoids, alkaloids, tannins, saponins, and other metabolites, have attracted considerable attention due to their central role in synthesizing nanomaterials with various biomedical applications. Hemicelluloses are the second most abundant among naturally occurring heteropolymers, accounting for one-third of all plant constituents. In particular, xylans, mannans, and arabinoxylans are structured polysaccharides derived from hemicellulose. Mannans and xylans are characterized by their linear configuration of β-1,4-linked mannose and xylose units, respectively. At the same time, arabinoxylan is a copolymer of arabinose and xylose found predominantly in secondary cell walls of seeds, dicotyledons, grasses, and cereal tissues. Their widespread use in tissue engineering, drug delivery, and gene delivery is based on their properties, such as cell adhesiveness, cost-effectiveness, high biocompatibility, biodegradability, and low immunogenicity. Moreover, it can be easily functionalized, which expands their potential applications and provides them with structural diversity. This review comprehensively addresses recent advances in the field of biomedical applications. It explores the potential prospects for exploiting the capabilities of mannans and xylans in drug delivery, gene delivery, and tissue engineering.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"261-277"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905241","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":"Surface Functionalized Lipid Nanoparticles in Promoting Therapeutic Outcomes: An Insight View of the Dynamic Drug Delivery System.","authors":"Namish Manchanda, Harish Vishkarma, Muskan Goyal, Saurabh Shah, Paras Famta, Sushama Talegaonkar, Saurabh Srivastava","doi":"10.2174/0113894501285598240216065627","DOIUrl":"10.2174/0113894501285598240216065627","url":null,"abstract":"<p><p>Compared to the conventional approach, nanoparticles (NPs) facilitate a non-hazardous, non-toxic, non-interactive, and biocompatible system, rendering them incredibly promising for improving drug delivery to target cells. When that comes to accomplishing specific therapeutic agents like drugs, peptides, nucleotides, <i>etc.</i>, lipidic nanoparticulate systems have emerged as even more robust. They have asserted impressive ability in bypassing physiological and cellular barriers, evading lysosomal capture and the proton sponge effect, optimizing bioavailability, and compliance, lowering doses, and boosting therapeutic efficacy. However, the lack of selectivity at the cellular level hinders its ability to accomplish its potential to the fullest. The inclusion of surface functionalization to the lipidic NPs might certainly assist them in adapting to the basic biological demands of a specific pathological condition. Several ligands, including peptides, enzymes, polymers, saccharides, antibodies, <i>etc</i>., can be functionalized onto the surface of lipidic NPs to achieve cellular selectivity and avoid bioactivity challenges. This review provides a comprehensive outline for functionalizing lipid-based NPs systems in prominence over target selectivity. Emphasis has been put upon the strategies for reinforcing the therapeutic performance of lipidic nano carriers' using a variety of ligands alongside instances of relevant commercial formulations.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"278-300"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971195","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":"Comparative Analysis of Circular RNAs Expression and Function between Aortic and Intracranial Aneurysms.","authors":"Ilgiz Gareev, Ozal Beylerli, Aamir Ahmad, Tatiana Ilyasova, Huaizhang Shi, Vladimir Chekhonin","doi":"10.2174/0113894501319306240819052840","DOIUrl":"10.2174/0113894501319306240819052840","url":null,"abstract":"<p><p>An aneurysm is an abnormal enlargement or bulging of the wall of a blood vessel. Most often, aneurysms occur in large blood vessels - the aorta (Thoracic Aortic Aneurysm (TAA) and Abdominal Aortic Aneurysm (AAA)) and brain vessels (Intracranial Aneurysm (IA)). Despite the presence of significant differences in the pathogenesis of the development and progression of IA and TAA/AAA, there are also similarities. For instance, both have been shown to be strongly influenced by shear stress, inflammatory processes, and enzymatic destruction of the elastic lamellae and extracellular matrix (ECM) proteins of the vascular wall. Moreover, although IA and TAA are predominantly considered arteriopathies with different pathological mechanisms, they share risk factors with AAA, such as hypertension and smoking. However, there is a need for a more in- -depth study of the key elements that may influence the formation and progression of a particular aneurysm to find ways of therapeutic intervention or search for a diagnostic tool. Today, it is known that the disruption of gene expression is one of the main mechanisms that contribute to the development of aneurysms. At the same time, growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of aneurysms. Although much has been studied of the known protein-coding genes, circular RNAs (circRNAs), a relatively new and rapidly evolving large family of transcripts, have recently received much scientific attention. CircRNAs regulate gene expression through the sponging of microRNAs (miRNAs) and can also be used as therapeutic targets and biomarkers. Increasing evidence has implicated circRNAs in the pathogenesis of multiple cardiovascular diseases, including the development of aneurysms. However, the mechanism of dysregulation of certain circRNAs in a particular aneurysm remains to be studied. The discovery of circRNAs has recently advanced our understanding of the latest mode of miRNAs/target genes regulation in the development and progression of IA and TAA/AAA. The aim of this study is to compare the expression profiles of circRNAs to search for similar or different effects of certain circRNAs on the formation and progression of IA and TAA/AAA.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"866-884"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine for Targeted Therapy of Lung Cancer: Advances and Developments.","authors":"Suraj Kumar, Rishabha Malviya, Prerna Uniyal","doi":"10.2174/0113894501306103240426131249","DOIUrl":"10.2174/0113894501306103240426131249","url":null,"abstract":"<p><p>Considering that lung cancer is a leading global perpetrator, novel treatment approaches must be investigated. Due to the broad spectrum of lung cancer, conventional therapies including chemotherapy, radiotherapy, and surgeries, are not always effective and can have adverse consequences. The present study's overarching objective was to enhance the development of a personalized vaccine for targeted lung cancer therapy. Vaccination functions by eliciting a strong and targeted immune response defense by taking advantage of the specific antigens that are expressed by lung cancer cells. Crucial antigens associated with tumor cells have been identified with the recognition of the genetic and immunological circumstances of lung cancer in this review. The vaccine includes these antigens to prime the immune system, directing it toward recognizing and attacking cancerous cells. In this review, we have addressed the possible benefits of a targeted vaccine strategy, which include a reduction in off-target effects and an improvement in health outcomes for patients. These studies highlight the promise of a tailored vaccine in a novel way for the treatment of lung cancer. The integration of molecular profiling and immunological insights offers a rationale for the design and implementation of personalized vaccines. While challenges exist, the promise of improved treatment outcomes and reduced side effects positions targeted vaccine therapy as a compelling avenue for advancing lung cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"526-529"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847234","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":"Polymeric Micelle-Based Nanogels as Emerging Drug Delivery Systems in Breast Cancer Treatment: Promises and Challenges.","authors":"M Yazdan, S M Naghib, M R Mozafari","doi":"10.2174/0113894501294136240610061328","DOIUrl":"10.2174/0113894501294136240610061328","url":null,"abstract":"<p><p>Breast cancer is a pervasive global health issue that disproportionately impacts the female population. Over the past few years, there has been considerable interest in nanotechnology due to its potential utility in creating drug-delivery systems designed to combat this illness. The primary aim of these devices is to enhance the delivery of targeted medications, optimise the specific cells that receive the drugs, tackle treatment resistance in malignant cells, and introduce novel strategies for preventing and controlling diseases. This research aims to examine the methodologies utilised by various carrier nanoparticles in the context of therapeutic interventions for breast cancer. The main objective is to investigate the potential application of novel delivery technologies to attain timely and efficient diagnosis and treatment. Current cancer research predominantly examines diverse drug delivery methodologies for chemotherapeutic agents. These methodologies encompass the development of hydrogels, micelles, exosomes, and similar compounds. This research aims to analyse the attributes, intricacies, notable advancements, and practical applications of the system in clinical settings. Despite the demonstrated efficacy of these methodologies, an apparent discrepancy can be observed between the progress made in developing innovative therapeutic approaches and their widespread implementation in clinical settings. It is critical to establish a robust correlation between these two variables to enhance the effectiveness of medication delivery systems based on nanotechnology in the context of breast cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"649-669"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449940","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":"Bile Acid Application in Cell-Targeting for Molecular Receptors in Relation to Hearing: A Comprehensive Review.","authors":"Corina M Ionescu, Melissa A Jones, Susbin R Wagle, Bozica Kovacevic, Thomas Foster, Momir Mikov, Armin Mooranian, Hani Al-Salami","doi":"10.2174/0113894501278292231223035733","DOIUrl":"10.2174/0113894501278292231223035733","url":null,"abstract":"<p><p>Bile acids play important roles in the human body, and changes in their pool can be used as markers for various liver pathologies. In addition to their functional effects in modulating inflammatory responses and cellular survivability, the unconjugated or conjugated, secondary, or primary nature of bile acids accounts for their various ligand effects. The common hydrophilic bile acids have been used successfully as local treatment to resolve drug-induced cell damage or to ameliorate hearing loss. From various literature references, bile acids show concentration and tissue-dependent effects. Some hydrophobic bile acids act as ligands modulating vitamin D receptors, muscarinic receptors, and calcium-activated potassium channels, important proteins in the inner ear system. Currently, there are limited resources investigating the therapeutic effects of bile acid on hearing loss and little to no information on detecting bile acids in the remote ear system, let alone baseline bile acid levels and their prevalence in healthy and disease conditions. This review presents both hydrophilic and hydrophobic human bile acids and their tissue-specific effects in modulating cellular integrity, thus considering the possible effects and extended therapeutic applicability of bile acids to the inner ear tissue.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"158-170"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402143","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":"Exploring the Efficient Natural Products for the Therapy of Parkinson's Disease <i>via Drosophila Melanogaster</i> (Fruit Fly) Models.","authors":"Wen Zhang, Yingjie Ju, Yunuo Ren, Yaodong Miao, Yiwen Wang","doi":"10.2174/0113894501281402231218071641","DOIUrl":"10.2174/0113894501281402231218071641","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a severe neurodegenerative disorder, partly attributed to mutations, environmental toxins, oxidative stress, abnormal protein aggregation, and mitochondrial dysfunction. However, the precise pathogenesis of PD and its treatment strategy still require investigation. Fortunately, natural products have demonstrated potential as therapeutic agents for alleviating PD symptoms due to their neuroprotective properties. To identify promising lead compounds from herbal medicines' natural products for PD management and understand their modes of action, suitable animal models are necessary. <i>Drosophila melanogaster</i> (fruit fly) serves as an essential model for studying genetic and cellular pathways in complex biological processes. Diverse <i>Drosophila</i> PD models have been extensively utilized in PD research, particularly for discovering neuroprotective natural products. This review emphasizes the research progress of natural products in PD using the fruit fly PD model, offering valuable insights into utilizing invertebrate models for developing novel anti-PD drugs.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"77-93"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424490","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 Targets and Mechanisms of Hedyotis diffusa Willd. for Esophageal Adenocarcinoma Treatment Based on Network Pharmacology and Weighted Gene Co-expression Network Analysis.","authors":"Yu Zhuang, Yun-Gang Sun, Chen-Guang Wang, Qiang Zhang, Chao Che, Feng Shao","doi":"10.2174/0113894501265851240102101122","DOIUrl":"10.2174/0113894501265851240102101122","url":null,"abstract":"<p><strong>Background: </strong>Hedyotis diffusa Willd. (HDW) is a common anticancer herbal medicine in China, and its therapeutic effectiveness has been demonstrated in a range of cancer patients. There is no consensus about the therapeutic targets and molecular mechanisms of HDW, which contains many active ingredients.</p><p><strong>Aim: </strong>To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA).</p><p><strong>Methods: </strong>The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1.</p><p><strong>Result: </strong>Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.</p><p><strong>Conclusion: </strong>Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"431-443"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424491","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 Insights into Carpal Tunnel Syndrome: Clinical Strategies for Prevention and Treatment.","authors":"Rishabh Chaudhary, Janvi Khanna, Seema Bansal, Nitin Bansal","doi":"10.2174/0113894501280331240213063333","DOIUrl":"10.2174/0113894501280331240213063333","url":null,"abstract":"<p><strong>Background: </strong>Carpal tunnel syndrome (CTS) is a condition that is caused by medial nerve compression, resulting in symptoms such as numbness, tightness, or weakness in the hand.</p><p><strong>Objectives: </strong>The aim of the study was to find out the genetic modulation, mechanism, available treatment, and recommendation for carpal tunnel syndrome at its specific stage.</p><p><strong>Methods: </strong>Almost 200 papers were searched for this review article, and 145 articles were selected. The literature was collected from different sources like Google scholar, PubMed, a directory of open-access journals, and science.gov by using keywords, such as treatment, risk factors, recommendation, and clinical features of carpal tunnel syndrome.</p><p><strong>Results: </strong>The most efficient non-surgical treatment is methylprednisolone acetate, which reduces inflammation by acting on the glucocorticoid receptor in conjunction with immunofilling. It has also been used successfully as a second-line drug for the treatment of patients with mild or moderate conditions in order to provide relief. New non-pharmacological options include laser therapy in acupuncture, transcutaneous electric nerve stimulation (TENS), and sham therapy. Modern treatments like TENS, laser therapy, splints, and injections of methylprednisolone acetate have been demonstrated to be helpful in sporadic situations. For patients with mild and moderate problems, more research should be conducted that includes the combination of these surgical and non-surgical treatments.</p><p><strong>Conclusion: </strong>We propose a multifunctional panel construct and define standard data items for future research into carpal tunnel syndrome. A discussion on idiopathic carpal tunnel syndrome, risk factors, combination of therapies, using guidelines-based recommendations and treatment should be initiated.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"221-240"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930436","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}