Expert Opinion on Therapeutic Targets最新文献_第5页

Synaptic fidelity for drug development: is it time to move beyond glutamate release and receptors? 药物开发中的突触保真度：是超越谷氨酸释放和受体的时候了吗？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-06 DOI: 10.1080/14728222.2024.2389201

Chadi G Abdallah, Amanda J F Tamman

引用次数: 0

Uterine fibroids: current research on novel drug targets and innovative therapeutic strategies. 子宫肌瘤：目前对新型药物靶点和创新治疗策略的研究。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-13 DOI: 10.1080/14728222.2024.2390094

Michal Ciebiera, Jakub Kociuba, Mohamed Ali, Obianuju Sandra Madueke-Laveaux, Qiwei Yang, Monika Bączkowska, Marta Włodarczyk, Natalia Żeber-Lubecka, Elżbieta Zarychta, Ana Corachán, Samar Alkhrait, Vafaei Somayeh, Iana Malasevskaia, Tomasz Łoziński, Piotr Laudański, Robert Spaczynski, Grzegorz Jakiel, Ayman Al-Hendy

{"title":"Uterine fibroids: current research on novel drug targets and innovative therapeutic strategies.","authors":"Michal Ciebiera, Jakub Kociuba, Mohamed Ali, Obianuju Sandra Madueke-Laveaux, Qiwei Yang, Monika Bączkowska, Marta Włodarczyk, Natalia Żeber-Lubecka, Elżbieta Zarychta, Ana Corachán, Samar Alkhrait, Vafaei Somayeh, Iana Malasevskaia, Tomasz Łoziński, Piotr Laudański, Robert Spaczynski, Grzegorz Jakiel, Ayman Al-Hendy","doi":"10.1080/14728222.2024.2390094","DOIUrl":"10.1080/14728222.2024.2390094","url":null,"abstract":"Introduction: Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy.Areas covered: This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy.Expert opinion: While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"669-687"},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970930","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}

引用次数: 0

Targeting ALK receptors in non-small cell lung cancer: what is the road ahead? 以非小细胞肺癌中的 ALK 受体为靶点：前路如何？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-19 DOI: 10.1080/14728222.2024.2389192

Paolo Maione, Valentina Palma, Giuseppina Pucillo, Cesare Gridelli

{"title":"Targeting ALK receptors in non-small cell lung cancer: what is the road ahead?","authors":"Paolo Maione, Valentina Palma, Giuseppina Pucillo, Cesare Gridelli","doi":"10.1080/14728222.2024.2389192","DOIUrl":"10.1080/14728222.2024.2389192","url":null,"abstract":"Introduction: Anaplastic lymphoma kinase (ALK) gene-rearrangements are identified in about 3-5% of non-small cell lung cancers (NSCLC), and ALK-rearranged NSCLC is to be considered an oncogene-addicted cancer with peculiar clinical characteristics.Areas covered: Several ALK inhibitors have been studied and approved for use in the treatment of advanced ALK-rearranged NSCLC with reported superiority in terms of efficacy and safety profile compared with chemotherapy. Second- and third-generation ALK inhibitors (alectinib, brigatinib, and lorlatinib) offer to NSCLC patients a clinically meaningful prolongment of survival with a very good quality of life profile. However, resistances to these agents always occur, with less satisfying options for second-line treatments. Direct comparisons among these agents are not available, and the choice among brigatinib, alectinib, and lorlatinib as first-line treatment remains challenging. Very recently, alectinib has been demonstrated to improve efficacy outcomes compared with chemotherapy also in resected stage IB-IIIA ALK-rearranged NSCLC, extending the clinical benefit offered by ALK inhibitors also to the adjuvant setting.Expert opinion: Future development of ALK inhibitors in NSCLC treatment includes the search for optimal management of acquired resistance to first-line treatments and the extension of use of ALK inhibitors also to neoadjuvant and preferably to perioperative setting.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"659-668"},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003988","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}

引用次数: 0

VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress. 作为神经退行性疾病潜在靶点的 VPS35 或 retromer：前进的障碍。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-22 DOI: 10.1080/14728222.2024.2392700

Anika Wu, Daehoon Lee, Wen-Cheng Xiong

{"title":"VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.","authors":"Anika Wu, Daehoon Lee, Wen-Cheng Xiong","doi":"10.1080/14728222.2024.2392700","DOIUrl":"10.1080/14728222.2024.2392700","url":null,"abstract":"Introduction: Vacuolar Protein Sorting 35 (VPS35) is pivotal in the retromer complex, governing transmembrane protein trafficking within cells, and its dysfunction is implicated in neurodegenerative diseases. A missense mutation, Asp620Asn (D620N), specifically ties to familial late-onset Parkinson's, while reduced VPS35 levels are observed in Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and tauopathies. VPS35's absence in certain neurons during development can initiate neurodegeneration, highlighting its necessity for neural health. Present therapeutic research mainly targets the clearance of harmful protein aggregates and symptom management. Innovative treatments focusing on VPS35 are under investigation, although fully understanding the mechanisms and optimal targeting strategies remain a challenge.Areas covered: This review offers a detailed account of VPS35's discovery, its role in neurodegenerative mechanisms - especially in Parkinson's and Alzheimer's - and its link to other disorders. It shines alight on recent insights into VPS35's function in development, disease, and as a therapeutic target.Expert opinion: VPS35 is integral to cellular function and disease association, making it a significant candidate for developing therapies. Progress in modulating VPS35's activity may lead to breakthrough treatments that not only slow disease progression but may also act as biomarkers for neurodegeneration risk, marking a step forward in managing these complex conditions.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"701-712"},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035561","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}

引用次数: 0

Ways of modulating GABA transporters to treat neurological disease. 调节 GABA 转运体以治疗神经系统疾病的方法。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-27 DOI: 10.1080/14728222.2024.2383611

Jonas S Mortensen, Amalie N L Mikkelsen, Petrine Wellendorph

{"title":"Ways of modulating GABA transporters to treat neurological disease.","authors":"Jonas S Mortensen, Amalie N L Mikkelsen, Petrine Wellendorph","doi":"10.1080/14728222.2024.2383611","DOIUrl":"10.1080/14728222.2024.2383611","url":null,"abstract":"Introduction: The main inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), is involved in a multitude of neurological and psychiatric disorders characterized by an imbalance in excitatory and inhibitory signaling. Regulation of extracellular levels of GABA is maintained by the four GABA transporters (GATs; GAT1, GAT2, GAT3, and BGT1), Na+/Cl--coupled transporters of the solute carrier 6 (SLC6) family. Despite mounting evidence for the involvement of the non-GAT1 GABA transporters in diseases, only GAT1 has successfully been translated into clinical practice via the drug tiagabine.Areas covered: In this review, all four GATs will be described in terms of their involvement in disease, and the most recent data on structure, function, expression, and localization discussed in relation to their potential role as drug targets. This includes an overview of various ways to modulate the GATs in relation to treatment of diseases caused by imbalances in the GABAergic system.Expert opinion: The recent publication of various GAT1 structures is an important milestone for future development of compounds targeting the GATs. Such information can provide much needed insight into mechanistic aspects of all GAT subtypes and be utilized to design improved ligands for this highly interesting drug target class.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"529-543"},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787705","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}

引用次数: 0

Antibacterial carbonic anhydrase inhibitors targeting Vibrio cholerae enzymes. 针对霍乱弧菌酶的抗菌碳酸酐酶抑制剂。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-19 DOI: 10.1080/14728222.2024.2369622

Mohammad Sadegh Gheibzadeh, Clemente Capasso, Claudiu T Supuran, Reza Zolfaghari Emameh

{"title":"Antibacterial carbonic anhydrase inhibitors targeting Vibrio cholerae enzymes.","authors":"Mohammad Sadegh Gheibzadeh, Clemente Capasso, Claudiu T Supuran, Reza Zolfaghari Emameh","doi":"10.1080/14728222.2024.2369622","DOIUrl":"10.1080/14728222.2024.2369622","url":null,"abstract":"Introduction: Cholera is a bacterial diarrheal disease caused by pathogen bacteria Vibrio cholerae, which produces the cholera toxin (CT). In addition to improving water sanitation, oral cholera vaccines have been developed to control infection. Besides, rehydration and antibiotic therapy are complementary treatment strategies for cholera. ToxT regulatory protein activates transcription of CT gene, which is enhanced by bicarbonate (HCO3-).Areas covered: This review delves into the genomic blueprint of V. cholerae, which encodes for α-, β-, and γ- carbonic anhydrases (CAs). We explore how the CAs contribute to the pathogenicity of V. cholerae and discuss the potential of CA inhibitors in mitigating the disease's impact.Expert opinion: CA inhibitors can reduce the virulence of bacteria and control cholera. Here, we reviewed all reported CA inhibitors, noting that α-CA from V. cholerae (VchCAα) was the most effective inhibited enzyme compared to the β- and γ-CA families (VchCAβ and VchCAγ). Among the CA inhibitors, acyl selenobenzenesulfonamidenamides and simple/heteroaromatic sulfonamides were the best VchCA inhibitors in the nM range. It was noted that some antibacterial compounds show good inhibitory effects on all three bacterial CAs. CA inhibitors belonging to other classes may be synthesized and tested on VchCAs to harness cholera.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"623-635"},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723324","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}

引用次数: 0

Epigenetic regulation of immune cells in systemic lupus erythematosus: insight from chromatin accessibility. 系统性红斑狼疮免疫细胞的表观遗传调控：从染色质可及性中窥见一斑。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1080/14728222.2024.2375372

Zhao-Xing Gao, Tian He, Peng Zhang, Xiao Hu, Man Ge, Yi-Qing Xu, Peng Wang, Hai-Feng Pan

{"title":"Epigenetic regulation of immune cells in systemic lupus erythematosus: insight from chromatin accessibility.","authors":"Zhao-Xing Gao, Tian He, Peng Zhang, Xiao Hu, Man Ge, Yi-Qing Xu, Peng Wang, Hai-Feng Pan","doi":"10.1080/14728222.2024.2375372","DOIUrl":"10.1080/14728222.2024.2375372","url":null,"abstract":"Introduction: Systemic Lupus Erythematosus (SLE) is a multi-dimensional autoimmune disease involving numerous tissues throughout the body. The chromatin accessibility landscapes in immune cells play a pivotal role in governing their activation, function, and differentiation. Aberrant modulation of chromatin accessibility in immune cells is intimately associated with the onset and progression of SLE.Areas covered: In this review, we described the chromatin accessibility landscapes in immune cells, summarized the recent evidence of chromatin accessibility related to the pathogenesis of SLE, and discussed the potential of chromatin accessibility as a valuable option to identify novel therapeutic targets for this disease.Expert opinion: Dynamic changes in chromatin accessibility are intimately related to the pathogenesis of SLE and have emerged as a new direction for exploring its epigenetic mechanisms. The differently accessible chromatin regions in immune cells often contain binding sites for transcription factors (TFs) and cis-regulatory elements such as enhancers and promoters, which may be potential therapeutic targets for SLE. Larger scale cohort studies and integrating epigenomic, transcriptomic, and metabolomic data can provide deeper insights into SLE chromatin biology in the future.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"637-649"},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467268","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}

引用次数: 0

Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury. PDE4B抑制剂在脂肪组织功能障碍和慢性肝损伤中的治疗前景。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-06-19 DOI: 10.1080/14728222.2024.2369590

Dalton W Staller, Robert G Bennett, Ram I Mahato

{"title":"Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.","authors":"Dalton W Staller, Robert G Bennett, Ram I Mahato","doi":"10.1080/14728222.2024.2369590","DOIUrl":"10.1080/14728222.2024.2369590","url":null,"abstract":"Introduction: Chronic liver disease (CLD) is a complex disease associated with profound dysfunction. Despite an incredible burden, the first and only pharmacotherapy for metabolic-associated steatohepatitis was only approved in March of this year, indicating a gap in the translation of preclinical studies. There is a body of preclinical work on the application of phosphodiesterase 4 inhibitors in CLD, none of these molecules have been successfully translated into clinical use.Areas covered: To design therapies to combat CLD, it is essential to consider the dysregulation of other tissues that contribute to its development and progression. As such, proper therapies must combat this throughout the body rather than focusing only on the liver. To detail this, literature characterizing the pathogenesis of CLD was pulled from PubMed, with a particular focus placed on the role of PDE4 in inflammation and metabolism. Then, the focus is shifted to detailing the available information on existing PDE4 inhibitors.Expert opinion: This review gives a brief overview of some of the pathologies of organ systems that are distinct from the liver but contribute to disease progression. The demonstrated efficacy of PDE4 inhibitors in other human inflammatory diseases should earn them further examination for the treatment of CLD.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"545-573"},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327372","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}

引用次数: 0

The role of adipokines in the pathogenesis of psoriasis - a focus on resistin, omentin-1 and vaspin. 脂肪因子在银屑病发病机制中的作用--重点关注抵抗素、网织蛋白-1 和 vaspin。

IF 5.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-05 DOI: 10.1080/14728222.2024.2375373

Kajetan Kiełbowski, Estera Bakinowska, Aleksandra Wiktoria Bratborska, Andrzej Pawlik

{"title":"The role of adipokines in the pathogenesis of psoriasis - a focus on resistin, omentin-1 and vaspin.","authors":"Kajetan Kiełbowski, Estera Bakinowska, Aleksandra Wiktoria Bratborska, Andrzej Pawlik","doi":"10.1080/14728222.2024.2375373","DOIUrl":"10.1080/14728222.2024.2375373","url":null,"abstract":"Background: Psoriasis is a chronic immune-mediated skin condition with several types of manifestation, including psoriatic arthritis. In recent years, studies have demonstrated multiple molecules and mechanisms that play important roles in the pathophysiology of psoriasis. Studies have been conducted to determine the role of adipokines, bioactive peptides secreted by the adipose tissue, in the pathogenesis of inflammatory diseases. These studies have shown that adipokines are dysregulated in psoriasis and their abnormal expression profile could contribute to the inflammatory mechanisms observed in psoriasis.Areas covered: In this review, we discuss the immunomodulatory features of resistin, omentin-1, and vaspin, and discuss their potential involvement in the pathogenesis of psoriasis.Expert opinion: The adipokines resistin, omentin, and vaspin appear to be promising therapeutic targets in psoriasis. It is important to seek to block the action of resistin, either by blocking its receptors or by blocking its systemic effects with antibodies. In the case of omentin and vaspin, substances that are receptor mimetics of these adipokines should be sought and studies conducted of their analogues for the treatment of psoriasis. To introduce these therapies into clinical practice, multicentre clinical trials are required to confirm their efficacy and safety after initial studies in animal models.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"587-600"},"PeriodicalIF":5.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533973","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}

引用次数: 0

Potential of αvβ6 and αvβ1 integrin inhibition for treatment of idiopathic pulmonary fibrosis. αvβ6和αvβ1整合素抑制治疗特发性肺纤维化的潜力。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1080/14728222.2024.2375375

Serena Bellani, Philip L Molyneaux, Toby M Maher, Paolo Spagnolo

引用次数: 0