Current drug targets最新文献

{"title":"Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms.","authors":"Azam Hosseinzadeh, Rarnoosh Seirafianpour, Mohammad Sheibani, Maryam Taheri, Ali Jamshidi Naeini, Russel J Reiter, Saeed Mehrzadi","doi":"10.2174/0113894501360934250512052503","DOIUrl":"https://doi.org/10.2174/0113894501360934250512052503","url":null,"abstract":"<p><p>Melatonin, a master regulator of circadian rhythms and diverse physiological processes, exhibits complex interactions with various molecules. Sirtuins, a family of histone deacetylases, are key players in aging, stress responses, and metabolism and represent a critical target for melatonin. This review explores the multifaceted functions of melatonin and sirtuins, delving into the molecular mechanisms of their interaction. We further examine the impact of this synergy on various pathologies across different organs. Studies suggest that melatonin modulates SIRT1 and SIRT3 signaling pathways, offering protection in neurodegenerative, cardiovascular, skeletal, and pulmonary diseases, as well as renal and hepatic dysfunction. Additionally, melatonin-sirtuin interactions have been implicated in mitigating cancer development and promoting health in the female and male reproductive systems. Notably, the majority of studies across these systems demonstrate melatonin's ability to regulate SIRT1 and SIRT3 signaling, thereby alleviating associated pathologies. In conclusion, the intricate interplay between melatonin and, particularly, SIRT1 and SIRT3 emerges as a crucial modulator of diverse signaling pathways, with promising therapeutic implications for a wide range of diseases.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076506","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 Progression and Treatment Approaches for the Kidney Stone Management.","authors":"Kritika Sharma, Riya Nagpal, Lakshita Pandey, Mahima Mittal, Ajay Sharma, Ramji Lal Yadav, Ghanshyam das Gupta, Kalicharan Sharma","doi":"10.2174/0113894501346592250505050431","DOIUrl":"https://doi.org/10.2174/0113894501346592250505050431","url":null,"abstract":"<p><strong>Background: </strong>Kidney stones have always been a significant matter in the healthcare sector worldwide, with a high prevalence rate, especially in women. Urolithiasis is the solid mineral deposits in the renal calyces and kidney pelvis. Expounding upon the pathophysiology, various mechanisms such as supersaturation, crystallization, and aggregation are explored. Some new targets can potentially stop the disease's underlying cause that has been found.</p><p><strong>Aim: </strong>To compile the Recent Progression and treatment approaches for kidney stone management.</p><p><strong>Material and methods: </strong>A systematic review was conducted using a comprehensive literature search on the roles of osteopontin, vitamin D, nephrocalcin, and other factors in kidney stone formation in Google Scholar, PubMed, Elsevier, etc. OPN is a multifunctional protein that limits the formation of stones by participating in resorption. The other is the concentration of vitamin D, which raises calcium absorption and causes kidney stones to form. Further, the review encapsulates the spectrum of treatment approaches encompassing phytoconstituents, pharmacotherapy, and minimally invasive procedures, including surgical interventions.</p><p><strong>Results: </strong>From the Phytochemical-based literature survey, Rubicodifolin, L-ascorbic acid, Thymoquinone, etc, show promising activity in managing kidney stone. Apart from that, we have found such data that has been published in reputed journals. This synthetic drug-based approach shows traditional drug-based targeting. Where Nifedipine, Chlorthalidone, Allopurinol, etc, were used for symptomatic relief. Peptide-based approach reveals that several peptides for the treatment of kidney stone, where Lumasiran, a phase III clinical trial peptide molecule, targets glycolate oxidase and reduces calcium oxalate crystal levels.</p><p><strong>Conclusion: </strong>To implement more effective treatments, it is necessary to identify and develop a targeted therapy for the druggable targets. Various such druggable targets have been reported such as osteopontin which has come out as a protein with various functions including involvement in the inhibition of crystal adherence to the renal epithelium. Another such target is vitamin D and nephrocalcin.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981576","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":"IL-17 Antagonists as a Promising Therapeutic Modality for Hidradenitis Suppurativa.","authors":"Piotr K Krajewski, Jacek C Szepietowski","doi":"10.2174/0113894501349063250429052040","DOIUrl":"https://doi.org/10.2174/0113894501349063250429052040","url":null,"abstract":"","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955494","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":"Microwave-assisted Green Synthesis: An Approach for the Development of Anti-tubercular Agents.","authors":"Biswa Mohan Sahoo, Prafulla Nandi, Dipika Rani Sahu, Bimal Krisna Banik, Shikha Sharma, Balakumar Chandrasekaran, Nayaka Raghavendra Babu","doi":"10.2174/0113894501346600250414075741","DOIUrl":"https://doi.org/10.2174/0113894501346600250414075741","url":null,"abstract":"<p><p>Tuberculosis (TB) is a serious infectious disease that primarily affects the lungs but can also spread to the brain and spine. The highly pathogenic bacteria that causes TB is called Mycobacterium tuberculosis (Mtb). Usually, when an infected person coughs, sneezes, or speaks, the disease spreads through the air. TB is treatable with antibiotics, but it requires a long course of treatment, usually 6 to 9 months to eliminate the bacteria and prevent drug resistance. Thus, developing novel anti-tubercular therapeutics with various structural classes is necessary to solve the problems brought on by strains that are resistant to several currently available therapies. Resistance to widely used anti-tubercular drugs is increasing daily. As a result, continuing medi-cation therapy is necessary to stop more microbial infections. However, it leads to treatment re-sistance, which increases the likelihood that the disease may resurface in immune-compromised patients. Several anti-tubercular medications with various molecular structures show appropriate anti-tubercular action against Mycobacterium TB strains that are drug-sensitive and drug-resistant. Compared to conventional synthetic methods, synthetic reactions can be carried out more effec-tively and selectively under simple reaction conditions by employing microwave radiation. Mi-crowave-assisted organic synthesis (MAOS) is a useful method for increasing product yield and selectivity while accelerating the reaction rate for different types of organic synthesis. Several lead compounds with anti-tubercular properties that were synthesized using the microwave irradi-ation (MWI) approach are discussed in the current work.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972885","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":"Innovations in Antimalarial Drug Discovery: New Targets and Leads.","authors":"Neha Jeena, Lata Panicker, Inshad Ali Khan","doi":"10.2174/0113894501380738250414111540","DOIUrl":"https://doi.org/10.2174/0113894501380738250414111540","url":null,"abstract":"<p><p>Malaria control is severely hindered by a lack of effective treatment options and the rise of drug-resistant strains of the parasite. Despite the absence of a reliable vaccine, the thera-peutic application of antimalarial drugs remains the primary strategy for controlling and prevent-ing malaria. However, most existing antimalarial drugs target the blood stage of the parasite's lifecycle and may not effectively eliminate liver-stage parasites, limiting their efficacy in com-plete parasite clearance. The urgent need for novel antimalarial drugs with innovative mecha-nisms of action is critical to preventing a major public health crisis. Developing new antimalarial drugs involves both optimizing existing compounds and designing novel molecules that target unique biological pathways in Plasmodium. This review explores promising drug targets, includ-ing heme detoxification, food vacuole function, mitochondria, protein kinases, apicoplast path-ways, nucleic acid biosynthesis, fatty acid metabolism, the electron transport chain (ETC), and P-Type ATPases. Lead candidates targeting these mechanisms are discussed, highlighting their po-tential as next-generation antimalarial agents. Additionally, we provide updates on clinically vali-dated targets and the progress of antimalarial drug candidates in different stages of clinical devel-opment. Emerging therapeutic strategies focusing on malarial transporters, protein interaction networks, and substrate repertoires offer new avenues for drug discovery. A deeper understanding of these pathways can enhance drug efficacy, mitigate resistance, and support the development of long-lasting antimalarial therapies. This review aims to provide insights into the current landscape of antimalarial drug development and future directions for combating malaria.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982626","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 Understanding the Role of PEST Sequence-Containing Proteins in Retinal Neovascularization.","authors":"Yuxi Du, Yalong Dang","doi":"10.2174/0113894501383009250410081726","DOIUrl":"https://doi.org/10.2174/0113894501383009250410081726","url":null,"abstract":"<p><p>Recent studies have identified significant advancements in understanding the role of PEST sequence-containing proteins in retinal neovascularization. Retinal neovascularization, a critical pathological process, leads to severe visual impairment associated with conditions such as diabetic retinopathy, retinopathy of prematurity, and neovascular age-related macular degeneration. These conditions represent the leading causes of blindness worldwide. Although initially effective, current anti-VEGF treatments can lose efficacy over time and impose a burden due to frequent administrations, highlighting the need for novel therapeutic targets. PEST sequences, characterized by proline, glutamic acid, serine, and threonine enrichment, are structural motifs within proteins that target them for rapid degradation via the ubiquitin-proteasome pathway. Beyond influencing protein degradation, PEST sequences are crucial in regulating angiogenesis and inflammation, essential factors in retinal disease progression. This review focuses on the dual regulatory roles of PEST sequences in VEGFR-2 degradation and stabilization, crucial receptors in angiogenic signaling, as well as their involvement in essential signaling pathways including Notch and JAK/STAT. These findings suggest that PEST sequences could serve as promising new therapeutic targets to control pathological neovascularization and associated inflammatory responses, paving the way for more effective treatments in retinal diseases. Furthermore, advances in gene editing technologies and innovative drug delivery systems enhance the potential for the development of PEST sequence-targeted therapies, offering promising avenues for future clinical applications.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977779","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":"Quorum Sensing and its Inhibition in Pseudomonas aeruginosa: Molecular Targets and Mode of Action.","authors":"Dimple K Kachhadiya, John J Georrge","doi":"10.2174/0113894501373124250410105111","DOIUrl":"https://doi.org/10.2174/0113894501373124250410105111","url":null,"abstract":"<p><p>Biofilms are complicated microbial communities attached to surfaces, bringing about serious clinical, industrial, and environmental issues due to their resistance to conventional antimicrobial treatments. One critical factor of biofilm formation and persistence is quorum sensing - a mechanism that enables cell-to-cell communication and controls the gene expression pattern depending on the population density. It is based on the constant production, secretion, and response of small signalling molecules, termed auto-inducers. The main role of QS is the regulation of vital processes in the cell, such as biofilm formation and virulence factor production, which intensify pathogenicity, drug resistance, and toxin production. In this respect, interruption of QS can be a potential druggable target, and the discovery of QS-inhibiting agents as anti-virulence compounds may offer an alternative therapeutic approach to conventional antibiotics. Quorum sensing inhibition implies a novel strategy against microbial pathogenicity as it only reduces cell-to-cell communication pathways and thus attenuates various physiological responses coordinated by the QS mechanism. Hence, it qualifies as a suitable target for drug discovery. This article provides a comprehensive overview of the Las, Rhl, Pqs, and Iqs quorum sensing cascades in Pseudomonas aeruginosa, elucidating their molecular targets and regulatory roles in virulence. Focusing on therapeutic potential, the review highlights recently identified QS inhibitors and their mechanisms of action, focusing on molecular targets within QS cascades. The review underscores the critical importance of identifying key molecular targets within QS cascades, as their precise knowledge enables the strategic design of inhibitors that disrupt bacterial communication. This work advances innovative therapeutic paradigms by identifying key QS targets, offering promising strategies to disrupt virulence pathways and combat P. aeruginosa infections.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956912","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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","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":"Glutathione-responsive Nanoparticles for Optimized Cas9/sgRNA Gene Editing Delivery.","authors":"Md Sadique Hussain, Ajay Singh Bisht, Haider Ali, Gaurav Gupta","doi":"10.2174/0113894501370119250409074208","DOIUrl":"https://doi.org/10.2174/0113894501370119250409074208","url":null,"abstract":"","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981553","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":"https://doi.org/10.2174/0113894501347158250305074908","url":null,"abstract":"<p><strong>Background: </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":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","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}