Expert Opinion on Therapeutic Targets最新文献

{"title":"Fatty liver disease: time to target CCR5?","authors":"Vlad Dumitru Brata, Frank Tacke","doi":"10.1080/14728222.2024.2366880","DOIUrl":"10.1080/14728222.2024.2366880","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"335-339"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HIF-1α in sickle cell disease and cancer: unraveling therapeutic opportunities and risks.","authors":"Saba Ubaid, Mohammad Kashif, Yusra Laiq, Akshay Kumar Nayak, Vipin Kumar, Vivek Singh","doi":"10.1080/14728222.2024.2367640","DOIUrl":"10.1080/14728222.2024.2367640","url":null,"abstract":"<p><strong>Introduction: </strong>HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation.</p><p><strong>Areas covered: </strong>In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards.</p><p><strong>Expert opinion: </strong>Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"357-373"},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current challenges in the discovery of treatments against Mayaro fever.","authors":"Rafael Elias Marques, Jacqueline Farinha Shimizu, Maurício Lacerda Nogueira, Nikos Vasilakis","doi":"10.1080/14728222.2024.2351504","DOIUrl":"10.1080/14728222.2024.2351504","url":null,"abstract":"<p><strong>Introduction: </strong>Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems.</p><p><strong>Areas covered: </strong>We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies.</p><p><strong>Expert opinion: </strong>Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only <i>in vitro</i>. Compounds rarely progress to<i>in vivo</i> or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease <i>in vivo</i>, which might reduce long-term sequelae.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"345-356"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV Pol: does it offer therapeutic targets for HIV?","authors":"Camilla Muccini, Antonella Castagna","doi":"10.1080/14728222.2024.2351510","DOIUrl":"10.1080/14728222.2024.2351510","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"341-343"},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.","authors":"Tingting Li, Qussay Marashly, Jitae A Kim, Na Li, Mihail G Chelu","doi":"10.1080/14728222.2024.2351501","DOIUrl":"10.1080/14728222.2024.2351501","url":null,"abstract":"<p><strong>Introduction: </strong>The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output.</p><p><strong>Areas covered: </strong>In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field.</p><p><strong>Expert opinion: </strong>Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an I_f specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"385-400"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11395937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel benzimidazole angiotensin receptor blockers with anti-SARS-CoV-2 activity equipotent to that of nirmatrelvir: computational and enzymatic studies.","authors":"Harry Ridgway, Graham J Moore, Laura Kate Gadanec, Anthony Zulli, Vasso Apostolopoulos, Weronika Hoffmann, Katarzyna Węgrzyn, Niki Vassilaki, George Mpekoulis, Marios Zouridakis, Petros Giastas, Veroniki P Vidali, Konstantinos Kelaidonis, Minos-Timotheos Matsoukas, Marios Dimitriou, Thomas Mavromoustakos, Sotirios Tsiodras, Vassilis G Gorgoulis, Ioannis Karakasiliotis, Christos T Chasapis, John M Matsoukas","doi":"10.1080/14728222.2024.2362675","DOIUrl":"10.1080/14728222.2024.2362675","url":null,"abstract":"<p><strong>Background: </strong>Hypertension worsens outcomes in SARS-CoV-2 patients. Sartans, a type of antihypertensive angiotensin receptor blocker-(ARB), reduce COVID-19 morbidity and mortality by targeting angiotensin-converting enzyme-2 (ACE2). This study aimed to evaluate the antiviral and antihypertensive effects of nirmatrelvir, commercial sartans (candesartan, losartan, and losartan carboxylic (Exp3174)), and newly synthesized sartans (benzimidazole-N-biphenyl carboxyl (ACC519C) and benzimidazole-N-biphenyl tetrazole (ACC519T)), compared to nirmatrelvir, the antiviral component of Paxlovid.</p><p><strong>Research design and methods: </strong>Surface plasmon resonance (SPR) and enzymatic studies assessed drug effects on ACE2. Antiviral abilities were tested with SARS-CoV-2-infected Vero E6 cells, and antihypertensive effects were evaluated using angiotensin II-contracted rabbit iliac arteries.</p><p><strong>Results: </strong>Benzimidazole-based candesartan and ACC519C showed antiviral activity comparable to nirmatrelvir (95% inhibition). Imidazole-based losartan, Exp3174, and ACC519T were less potent (75%-80% and 50%, respectively), with Exp3174 being the least effective. SPR analysis indicated high sartans-ACE2 binding affinity. Candesartan and nirmatrelvir combined had greater inhibitory and cytopathic effects (3.96%) than individually (6.10% and 5.08%). ACE2 enzymatic assays showed varying effects of novel sartans on ACE2. ACC519T significantly reduced angiotensin II-mediated contraction, unlike nirmatrelvir and ACC519T(2).</p><p><strong>Conclusion: </strong>This study reports the discovery of a new class of benzimidazole-based sartans that significantly inhibit SARS-CoV-2, likely due to their interaction with ACE2.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"437-459"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New targets and mechanisms of action for lipid-lowering and anti-inflammatory therapies in atherosclerosis: where does the field stand?","authors":"Stephen J Nicholls, Adam J Nelson","doi":"10.1080/14728222.2024.2362644","DOIUrl":"10.1080/14728222.2024.2362644","url":null,"abstract":"<p><strong>Introduction: </strong>Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide, despite widespread use of statins. There is a need to develop additional therapeutic strategies that will complement statins to achieve more effective reductions in cardiovascular risk.</p><p><strong>Areas covered: </strong>This review provides a comprehensive summary of current areas of therapeutic development targeting both lipid and inflammatory factors implicated in the pathogenesis of atherosclerosis. In addition to develop of novel approaches that will produce more effective lowering of low-density lipoprotein cholesterol, clinical trials are currently evaluating the potential to target other atherogenic lipid parameters such as triglyceride-rich lipoproteins and Lp(a), in addition to promoting the biological properties of high-density lipoproteins. Targeting inflammation within the vascular wall has emerged as a new frontier in cardiovascular prevention, with early evidence that use of anti-inflammatory agents have the potential to reduce cardiovascular risk.</p><p><strong>Expert opinion: </strong>Clinical practice has an increasing array of therapeutic tools to achieve more effective lowering of low-density lipoprotein cholesterol for high-risk patients. In addition, clinical trials have the potential to deliver a range of additional agents to the clinic, that target alternative lipid and inflammatory mediators. This will permit the potential to personalize cardiovascular prevention.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"375-384"},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100A1: a promising therapeutic target for heart failure","authors":"Dorothea Noll, Dorothea Kehr, Patrick Most, Julia Ritterhoff","doi":"10.1080/14728222.2024.2345746","DOIUrl":"https://doi.org/10.1080/14728222.2024.2345746","url":null,"abstract":"Published in Expert Opinion on Therapeutic Targets (Just accepted, 2024)","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"17 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular drilling to combat salmonella typhi biofilm using L-Asparaginase via multiple targeting process","authors":"Aditya Upadhyay, Dharm Pal, Awanish Kumar","doi":"10.1080/14728222.2024.2344699","DOIUrl":"https://doi.org/10.1080/14728222.2024.2344699","url":null,"abstract":"Salmonella Typhibiofilm condition is showing as a major public health problem due to the developmentof antibiotic resistance and less available druggable target proteins.Therefore, we aimed to iden...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"77 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Non-receptor tyrosine kinases in epilepsy: significance and potential as therapeutic targets","authors":"Ozasvi R Shanker, Sonali Kumar, Jyotirmoy Banerjee, Manjari Tripathi, P Sarat Chandra, Aparna Banerjee Dixit","doi":"10.1080/14728222.2024.2343952","DOIUrl":"https://doi.org/10.1080/14728222.2024.2343952","url":null,"abstract":"Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatmen...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"80 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140610282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}