Expert Opinion on Drug Discovery最新文献_第4页

The discovery and development of gefapixant as a novel antitussive therapy. 发现并开发了新型止咳疗法吉非匹克爽。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1080/17460441.2024.2391902

Maria Gabriella Matera, Paola Rogliani, Clive P Page, Luigino Calzetta, Mario Cazzola

{"title":"The discovery and development of gefapixant as a novel antitussive therapy.","authors":"Maria Gabriella Matera, Paola Rogliani, Clive P Page, Luigino Calzetta, Mario Cazzola","doi":"10.1080/17460441.2024.2391902","DOIUrl":"10.1080/17460441.2024.2391902","url":null,"abstract":"Introduction: Gefapixant, a P2X 3 receptor antagonist, shows considerable potential in managing refractory or unexplained chronic cough. Clinical trials have consistently demonstrated its efficacy in significantly reducing cough frequency and alleviating associated symptoms. However, its adverse effect profile, particularly taste disturbances such as dysgeusia and hypogeusia, the incidence of which is dose-dependent, poses a significant challenge to patient compliance and overall treatment satisfaction.Areas covered: The authors review the mechanism of action of gefapixant, the dose-dependent nature of its adverse effects and the findings from various clinical trials, including Phase 1, Phase 2, and Phase 3 studies. The authors also cover its regulatory status, post-marketing data, and its main competitors.Expert opinion: Gefapixant represents a significant advancement in treating chronic cough. However, balancing efficacy and tolerability is crucial. Lower effective doses and potential combination therapies may mitigate taste disturbances. Patient education and close monitoring during treatment are also important for optimal outcomes. Further research is needed to refine dosing strategies to minimize side effects while maintaining therapeutic efficacy. This research and personalized treatment approaches are key to optimizing gefapixant therapy, ensuring improved management of chronic cough while reducing adverse effects. However, pharmaceutical trials and proposals must be adapted to align with each regulatory body's specific requirements and concerns.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1159-1172"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975504","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

Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update. 用于肌萎缩性脊髓侧索硬化症药物研发的前景看好的动物模型：全面更新。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-08 DOI: 10.1080/17460441.2024.2387791

Léa Lescouzères, Shunmoogum A Patten

{"title":"Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update.","authors":"Léa Lescouzères, Shunmoogum A Patten","doi":"10.1080/17460441.2024.2387791","DOIUrl":"10.1080/17460441.2024.2387791","url":null,"abstract":"Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They have provided valuable insight into disease mechanisms and the development of therapeutic strategies.Areas covered: In this review, the authors provide a concise overview of simple genetic model organisms, including C. elegans, Drosophila, zebrafish, and mouse genetic models that have been generated to study ALS. They emphasize the benefits of each model and their application in translational research for discovering new chemicals, gene therapy approaches, and antibody-based strategies for treating ALS.Expert opinion: Significant progress is being made in identifying new therapeutic targets for ALS. This progress is being enabled by promising animal models of the disease using increasingly effective genetic and pharmacological strategies. There are still challenges to be overcome in order to achieve improved success rates for translating drugs from animal models to clinics for treating ALS. Several promising future directions include the establishment of novel preclinical protocol standards, as well as the combination of animal models with human induced pluripotent stem cells (iPSCs).","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1213-1233"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901476","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

Correction. 更正。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-19 DOI: 10.1080/17460441.2024.2392351

引用次数: 0

Targeting polo-like kinase 1: advancements and future directions in anti-cancer drug discovery. 靶向多聚样激酶 1：抗癌药物研发的进展与未来方向。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-07-29 DOI: 10.1080/17460441.2024.2385603

Monika Raab, Sven Becker, Mourad Sanhaji

引用次数: 0

New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer? 强迫症药物研发的新视野：谷氨酸受体是答案吗？

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI: 10.1080/17460441.2024.2387127

Giacomo Grassi, Edoardo Scillitani, Chiara Cecchelli

{"title":"New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer?","authors":"Giacomo Grassi, Edoardo Scillitani, Chiara Cecchelli","doi":"10.1080/17460441.2024.2387127","DOIUrl":"10.1080/17460441.2024.2387127","url":null,"abstract":"Introduction: Over the past decade, glutamate has emerged as a prominent focus in the field of obsessive-compulsive disorder (OCD) pathophysiology. A convergence of evidence from genetic, preclinical, and clinical studies points to glutamatergic dysfunction as a key feature of this condition. In light of these findings, there has been a growing interest in exploring the potential of glutamatergic agents in the treatment of OCD.Areas covered: This paper reviews the literature on glutamate transmission in OCD. In addition, the authors examine the results of clinical trials investigating the efficacy of glutamatergic agents in the treatment of OCD patients.Expert opinion: Along with the recognition of neuroinflammation in the brain in OCD, the evidence of glutamate dysfunction represents one of the most promising recent discoveries for understanding the mechanisms involved in OCD. The importance of this discovery lies primarily in its pharmacological implications and has led to intense research activity in the field of glutamatergic agents. While this research has not yet had a substantial clinical impact, targeting glutamate receptors remains a promising horizon for the successful treatment of OCD patients.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1235-1245"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893221","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

Opportunities and challenges with G-quadruplexes as promising targets for drug design. 将 G 型四联体作为有前途的药物设计目标的机遇与挑战。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-18 DOI: 10.1080/17460441.2024.2404230

Victoria Sanchez-Martin

{"title":"Opportunities and challenges with G-quadruplexes as promising targets for drug design.","authors":"Victoria Sanchez-Martin","doi":"10.1080/17460441.2024.2404230","DOIUrl":"https://doi.org/10.1080/17460441.2024.2404230","url":null,"abstract":"INTRODUCTIONG-quadruplexes (G4s) are secondary structures formed in guanine-rich regions of nucleic acids (both DNA and RNA). G4s are significantly enriched at regulatory genomic regions and are associated with important biological processes ranging from telomere homeostasis and genome instability to transcription and translation. Importantly, G4s are related to health and diseases such as cancer, neurological diseases, as well as infections with viruses and microbial pathogens. Increasing evidence suggests the potential of G4s for designing new diagnostic and therapeutic strategies although in vivo studies are still at early stages.AREAS COVEREDThis review provides an updated summary of the literature describing the impact of G4s in human diseases and different approaches based on G4 targeting in therapy.EXPERT OPINIONWithin the G4 field, most of the studies have been performed in vitro and in a descriptive manner. Therefore, detailed mechanistic understanding of G4s in the biological context remains to be deciphered. In clinics, the use of G4s as therapeutic targets has been hindered due to the low selectivity profile and poor drug-like properties of G4 ligands. Future research on G4s may overcome current methodological and interventional limitations and shed light on these unique structural elements in the pathogenesis and treatment of diseases.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"103 1","pages":"1-15"},"PeriodicalIF":6.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263068","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 progress and challenges in modeling colorectal cancer and the impact on novel drug discovery. 结直肠癌建模的进展和挑战以及对新药研发的影响。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-16 DOI: 10.1080/17460441.2024.2404238

Natália Teixeira, Ana Baião, Sofia Dias, Bruno Sarmento

{"title":"The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery.","authors":"Natália Teixeira, Ana Baião, Sofia Dias, Bruno Sarmento","doi":"10.1080/17460441.2024.2404238","DOIUrl":"https://doi.org/10.1080/17460441.2024.2404238","url":null,"abstract":"Introduction: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low. Traditional two-dimensional (2D) cell culture systems have been the foundation of cancer research, but their inability to replicate the complex tumor microenvironment (TME) limits their effectiveness.Areas covered: This paper explores the evolution of CRC models, starting with the limitations of traditional 2D cell culture systems and the significant advancements offered by 3D models. Additionally, it highlights 3D bioprinting and on-chip CRC models, which have enhanced the ability to mimic in vivo conditions.Expert opinion: The transition to advanced 3D models represents a pivotal shift in CRC research, offering considerable improvements over the established 2D models. These models hold promise for the development of patient-specific models that better mimic in vivo conditions. However, the inherent complexity of CRC continues to pose challenges in developing models that can fully capture the disease's multifaceted nature. This complexity and high costs associated with these technologies, along with the need for standardized protocols, pose significant challenges to their widespread adoption.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-10"},"PeriodicalIF":6.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282781","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

What are the translational challenges associated with Chagas disease drug discovery? 与南美锥虫病药物研发相关的转化挑战有哪些？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-13 DOI: 10.1080/17460441.2024.2402409

Inmaculada Ramírez-Macías,Paola García-Huertas,Clotilde Marín

引用次数: 0

Advances in the approaches used to repurpose drugs for neuroblastoma. 神经母细胞瘤药物再利用方法的进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-11 DOI: 10.1080/17460441.2024.2402413

Marta Miera-Maluenda,María Pérez-Torres,Adriana Mañas,Alba Rubio-San-Simón,Maria Butjosa-Espín,Paula Ruiz-Duran,Jose A Seoane,Lucas Moreno,Miguel F Segura

{"title":"Advances in the approaches used to repurpose drugs for neuroblastoma.","authors":"Marta Miera-Maluenda,María Pérez-Torres,Adriana Mañas,Alba Rubio-San-Simón,Maria Butjosa-Espín,Paula Ruiz-Duran,Jose A Seoane,Lucas Moreno,Miguel F Segura","doi":"10.1080/17460441.2024.2402413","DOIUrl":"https://doi.org/10.1080/17460441.2024.2402413","url":null,"abstract":"INTRODUCTIONNeuroblastoma (NB) remains a challenging pediatric malignancy with limited treatment options, particularly for high-risk cases. Drug repurposing offers a convenient and cost-effective strategy for treating rare diseases like NB. Using existing drugs with known safety profiles accelerates the availability of new treatments, reduces development costs, and mitigates risks, offering hope for improved patient outcomes in challenging conditions.AREAS COVEREDThis review provides an overview of the advances in approaches used to repurpose drugs for NB therapy. The authors discuss strategies employed in drug repurposing, including computational and experimental methods, and rational drug design, highlighting key examples of repurposed drugs with promising clinical results. Additionally, the authors examine the challenges and opportunities associated with drug repurposing in NB and discuss future directions and potential areas for further research.EXPERT OPINIONThe fact that only one new drug has been approved in the last 30 years for the treatment of neuroblastoma plus a significant proportion of high-risk NB patients that remain uncurable, evidences the need for new fast and cost-effective alternatives. Drug repurposing may accelerate the treatment development process while reducing expenses and risks. This approach can swiftly bring effective NB therapies to market, enhancing survival rates and patient quality of life.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"121 1","pages":"1-11"},"PeriodicalIF":6.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221469","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

Lessons learnt from broad-spectrum coronavirus antiviral drug discovery. 广谱冠状病毒抗病毒药物研发的经验教训。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI: 10.1080/17460441.2024.2385598

Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou

{"title":"Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.","authors":"Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou","doi":"10.1080/17460441.2024.2385598","DOIUrl":"10.1080/17460441.2024.2385598","url":null,"abstract":"Introduction: Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality.Areas covered: The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and lessons learnt in targeting viral non-structural proteins, structural proteins, drug repurposing, and combinational approaches for the development of antivirals against CoVs.Expert opinion: Drawing lessons from the pandemic, it becomes evident that the absence of efficient broad-spectrum antiviral drugs increases the vulnerability of public health systems to the potential onslaught by highly pathogenic CoVs. The rapid and sustained spread of novel CoVs can have devastating consequences without effective and specifically targeted treatments. Prioritizing the effective development of broad-spectrum antivirals is imperative for bolstering the resilience of public health systems and mitigating the potential impact of future highly pathogenic CoVs.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1023-1041"},"PeriodicalIF":6.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792329","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