Expert Opinion on Therapeutic Targets最新文献

The role of Nrf2 in immune cells and inflammatory autoimmune diseases: a comprehensive review. Nrf2 在免疫细胞和炎症性自身免疫疾病中的作用：全面综述。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-10 DOI: 10.1080/14728222.2024.2401518

Wang-Dong Xu,Chan Yang,An-Fang Huang

{"title":"The role of Nrf2 in immune cells and inflammatory autoimmune diseases: a comprehensive review.","authors":"Wang-Dong Xu,Chan Yang,An-Fang Huang","doi":"10.1080/14728222.2024.2401518","DOIUrl":"https://doi.org/10.1080/14728222.2024.2401518","url":null,"abstract":"INTRODUCTIONNrf2 regulates mild stress, chronic inflammation, and metabolic changes by regulating different immune cells via downstream signaling. Collection of information about the role of Nrf2 in inflammatory autoimmune diseases will better understand the therapeutic potential of targeting Nrf2 in these diseases.AREAS COVEREDIn this review, we comprehensively discussed biological function of Nrf2 in different immune cells, including Nrf2 preventing oxidative tissue injury, affecting apoptosis of immune cells and inflammatory cytokine production. Moreover, we discussed the role of Nrf2 in the development of inflammatory autoimmune diseases.EXPERT OPINIONNrf2 binds to downstream signaling molecules and then provides durable protection against different cellular and organ stress. It has emerged as an important target for inflammatory autoimmune diseases. Development of Nrf2 modulator drugs needs to consider factors such as target specificity, short/long term safety, disease indication identification, and the extent of variation in Nrf2 activity. We carefully discussed the dual role of Nrf2 in some diseases, which helps to better target Nrf2 in the future.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178925","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

Looking ahead to targeting macrophages by CAR T- or NK-cells in blood cancers. 展望在血癌中使用 CAR T 细胞或 NK 细胞靶向巨噬细胞。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-05 DOI: 10.1080/14728222.2024.2400075

David Kegyes, Paul Alexandru Milea, Andreea-Isabella Mazga, Adrian-Bogdan Tigu, Madalina Nistor, Diana Cenariu, Radu Tomai, Sanda Buruiana, Hermann Einsele, Alina Daniela Tănase, Ciprian Tomuleasa

{"title":"Looking ahead to targeting macrophages by CAR T- or NK-cells in blood cancers.","authors":"David Kegyes, Paul Alexandru Milea, Andreea-Isabella Mazga, Adrian-Bogdan Tigu, Madalina Nistor, Diana Cenariu, Radu Tomai, Sanda Buruiana, Hermann Einsele, Alina Daniela Tănase, Ciprian Tomuleasa","doi":"10.1080/14728222.2024.2400075","DOIUrl":"https://doi.org/10.1080/14728222.2024.2400075","url":null,"abstract":"Introduction: The bone marrow microenvironment (BME) is critical for healthy hematopoiesis and is often disrupted in hematologic malignancies. Tumor-associated macrophages (TAMs) are a major cell type in the tumor microenvironment (TME) and play a significant role in tumor growth and progression. Targeting TAMs and modulating their polarization is a promising strategy for cancer therapy.Areas covered: In this review, we discuss the importance of TME and different multiple possible targets to modulate immunosuppressive TAMs such as: CD123, Sphingosine 1-Phosphate Receptors, CD19/CD1d, CCR4/CCL22, CSF1R (CD115), CD24, CD40, B7 family proteins, MARCO, CD47, CD163, CD204, CD206 and folate receptors.Expert opinion: Innovative approaches to combat the immunosuppressive milieu of the tumor microenvironment in hematologic malignancies are of high clinical significance and may lead to increased survival, improved quality of life, and decreased toxicity of cancer therapies. Standard procedures will likely involve a combination of CAR T/NK-cell therapies with other treatments, leading to more comprehensive cancer care.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132258","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

An overview of Skp2: a promising new therapeutic target of psoriasis. Skp2概述：银屑病有望成为新的治疗靶点。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI: 10.1080/14728222.2024.2387604

Yashika Tomar, Moushumi Baidya, Jay Chadokiya, Shvetank Bhatt, Gautam Singhvi

{"title":"An overview of Skp2: a promising new therapeutic target of psoriasis.","authors":"Yashika Tomar, Moushumi Baidya, Jay Chadokiya, Shvetank Bhatt, Gautam Singhvi","doi":"10.1080/14728222.2024.2387604","DOIUrl":"10.1080/14728222.2024.2387604","url":null,"abstract":"Introduction: Psoriasis is a chronic immune-mediated disorder affecting over 2-3% of the population worldwide, significantly impacting quality of life. Despite the availability of various therapeutic interventions, concerns persist regarding lesion recurrence and potential alterations in immune surveillance promoting cancer progression. Recent advancements in understanding cellular and molecular pathways have unveiled key factors in psoriasis etiology, including IL-17, 22, 23, TNF-α, PDE-4, JAK-STAT inhibitors, and AhR agonists. This work explores the potential of S-phase kinase-associated protein 2 (Skp2) as a therapeutic target in psoriasis.Area covered: This review covers the current understanding of psoriasis pathophysiology, including immune dysregulation, and the role of keratinocytes and ubiquitin. It also delves into Skp2 role in cell cycle regulation, and its correlation with angiogenesis and ubiquitin in psoriasis. The evolving therapeutic approaches targeting Skp2, including small molecule inhibitors, are also discussed.Expert opinion: Targeting Skp2 holds promise for developing novel therapeutic approaches for psoriasis. By modulating Skp2 activity or expression, it may be possible to intervene in inflammatory and proliferative processes underlying the disease. Further research into Skp2 inhibitors and their efficacy in preclinical and clinical settings is warranted to harness the full potential of Skp2 as a therapeutic target in psoriasis management.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859466","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

The emerging role of Tetraspanin 32 in autoimmune diseases: from discovery to relevant theranostics? 四泛素 32 在自身免疫性疾病中的新作用：从发现到相关治疗？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-08-01 Epub Date: 2024-08-13 DOI: 10.1080/14728222.2024.2389203

Paolo Fagone, Katia Mangano, Ferdinando Nicoletti

引用次数: 0

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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"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

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":null,"pages":null},"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