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

Water in drug design: pitfalls and good practices. 药物设计中的水：陷阱和良好实践。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-06-01 Epub Date: 2025-04-27 DOI: 10.1080/17460441.2025.2497912

Balázs Zoltán Zsidó, Csaba Hetényi

{"title":"Water in drug design: pitfalls and good practices.","authors":"Balázs Zoltán Zsidó, Csaba Hetényi","doi":"10.1080/17460441.2025.2497912","DOIUrl":"10.1080/17460441.2025.2497912","url":null,"abstract":"Introduction: Structure-based drug design relies on optimizing drug-target interactions and blocking harmful pathophysiological events at the atomic level. Such events of the human body are modulated by water acting either as a medium or an individual partner in molecular interactions. A precise understanding of the modulatory mechanisms of water is essential for a successful drug design.Areas covered: The present review discusses different topographical and networking situations that result in radically different roles of water, a root of various pitfalls of drug design. The review surveys good practices for tackling the problems of determining water structure at atomic resolution. Techniques for quantifying the effects of bulk, networking, and individual water molecules on the stability of drug-target complexes are also discussed. The article is based on a literature search using the PubMed, Web of Science, and Google Scholar databases.Expert opinion: With advances in rapid computational algorithms and a better understanding of the physicochemical machinery of complex formation, theoretical approaches have resulted in elegant and cost-effective tools that fill the knowledge gaps left by the limited experimental methods. Overcoming the technical pitfalls of drug design, water transforms from a frustrating challenge into a handy tool for fine-tuning drug-target interactions.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"745-764"},"PeriodicalIF":6.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985637","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

In silico design strategies for tubulin inhibitors for the development of anticancer therapies. 微管蛋白抑制剂的芯片设计策略用于抗癌治疗的发展。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-30 DOI: 10.1080/17460441.2025.2507384

Ahmed Kamal, Prasanna Anjaneyulu Yakkala, Lakshmi Soukya, Sajeli Ahil Begum

{"title":"In silico design strategies for tubulin inhibitors for the development of anticancer therapies.","authors":"Ahmed Kamal, Prasanna Anjaneyulu Yakkala, Lakshmi Soukya, Sajeli Ahil Begum","doi":"10.1080/17460441.2025.2507384","DOIUrl":"10.1080/17460441.2025.2507384","url":null,"abstract":"Introduction: Microtubules, composing of α, β-tubulin dimers, are important for cellular processes like proliferation and transport, thereby they become suitable targets for research in cancer. Existing candidates often exhibit off-target effects, necessitating the quest for safer alternatives.Area covered: The authors explore various aspects of computer-aided drug design (CADD) for tubulin inhibitors. The authors review various techniques like molecular docking, QSAR analysis, molecular dynamic simulations, and machine learning approaches for predicting drug efficacy and modern computational methods utilized in the design and discovery of agents with anticancer potential. This article is based on a comprehensive search of literature utilizing Scopus, PubMed, Google Scholar, and Web of Science, covering the period from 2018 to 2025.Expert opinion: CADD is crucial in the pursuit of new cancer treatments, particularly by merging computer algorithms with experimental data. CADD predicts small molecule activity against tubulin related targets, expediting drug candidate identification and optimization for enhanced efficacy with reduced toxicity. Challenges include limited predictive models and the need for sophisticated ones to capture complex interactions among targets and pathways. Despite relying on cancer cell line transcriptome profiles, CADD remains pivotal for future anticancer drug discovery efforts.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-39"},"PeriodicalIF":6.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086069","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

Modeling potential drugs for Zika virus in animal and in vitro platforms: what is the current state of the art? 在动物和体外平台上对寨卡病毒潜在药物进行建模：目前的技术状况如何？

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1080/17460441.2025.2496461

Debora Santos, Nathalia Carrijo Oliveira, Elaine Cristina Alves Costa, Maria Vitória Ramalho Paes, Bruna Beltrão-Braga, Andrelissa Gorete Castanha, Patrícia Cristina Baleeiro Beltrão-Braga

{"title":"Modeling potential drugs for Zika virus in animal and in vitro platforms: what is the current state of the art?","authors":"Debora Santos, Nathalia Carrijo Oliveira, Elaine Cristina Alves Costa, Maria Vitória Ramalho Paes, Bruna Beltrão-Braga, Andrelissa Gorete Castanha, Patrícia Cristina Baleeiro Beltrão-Braga","doi":"10.1080/17460441.2025.2496461","DOIUrl":"https://doi.org/10.1080/17460441.2025.2496461","url":null,"abstract":"Introduction: The Zika virus (ZIKV) poses a significant public health threat due to its association with congenital Zika syndrome (CZS) and severe neurological disorders. Since its discovery, ZIKV has transitioned from sporadic outbreaks to a major epidemic in Brazil in 2015, which highlighted the urgent need for effective therapies, especially for vulnerable groups like pregnant women and newborns.Areas covered: This review provides a comprehensive overview of recent advancements in ZIKV drug discovery and their current stage of development, with a particular focus on those tested in animal models from 2018 to date, excluding vaccine candidates. Repurposed drugs, such as molnupiravir and sofosbuvir, have shown the potential to inhibit viral replication and mitigate disease. Novel compounds targeting viral proteins and host-directed therapies are also discussed. Furthermore, advanced in vitro models, including brain organoids, have offered critical insights into therapeutic efficacy.Expert opinion: Although some preclinical models have identified potential drugs ready for human translation, no protocol has yet been established for treating ZIKV infection. Currently, the treatment involves supportive care, managing symptoms, and preventing complications, especially for pregnant women. Ongoing research aims to develop specific antiviral therapies and vaccines; however, no such options are currently available.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"20 5","pages":"585-597"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975797","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 : 2025-05-01 Epub 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":"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":"565-574"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","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

Advancing target validation with PROTAC technology. 利用PROTAC技术推进目标验证。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-10 DOI: 10.1080/17460441.2025.2490248

M Leora Spitz, Aseel Kashkush, Raphael I Benhamou

{"title":"Advancing target validation with PROTAC technology.","authors":"M Leora Spitz, Aseel Kashkush, Raphael I Benhamou","doi":"10.1080/17460441.2025.2490248","DOIUrl":"10.1080/17460441.2025.2490248","url":null,"abstract":"Introduction: Targeted protein degradation (TPD) is a cutting-edge technology that provides new avenues for drug discovery and development. PROteolysis TArgeting Chimeras (PROTACs) are the most established and advanced TPD strategy, enabling the selective degradation of disease-associated and 'undruggable' proteins of interest (POIs) by leveraging the cell's natural protein degradation machinery. To confirm that PROTAC-induced proximity drives protein degradation, target validation and ternary complex formation must be thoroughly assessed.Areas covered: In this perspective, the authors detail some of the most widely used in silico, structural, in vitro, and in cellulo methods to validate PROTAC target engagement and ternary complex formation. Additionally, they discuss the growing use of PROTACs as chemical probes for novel target identification and validation.Expert opinion: Target validation is essential in the PROTAC approach, and ongoing studies should prioritize confirming ternary complex formation using assays conducted under physiologically relevant cellular conditions. Proteomics analyses are among the most valuable tools for elucidating PROTAC mechanisms, selectivity, and outcomes. The authors are optimistic about the future of PROTACs in drug development and their use as probes to confirm target engagement. PROTAC technology holds vast opportunities for future exploration, offering significant potential to further both chemical and biological research.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"551-563"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795079","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 update on knowledge graphs and their current and potential applications in drug discovery. 知识图谱的最新进展及其在药物发现中的当前和潜在应用。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-14 DOI: 10.1080/17460441.2025.2490253

Angela Serra, Michele Fratello, Antonio Federico, Dario Greco

{"title":"An update on knowledge graphs and their current and potential applications in drug discovery.","authors":"Angela Serra, Michele Fratello, Antonio Federico, Dario Greco","doi":"10.1080/17460441.2025.2490253","DOIUrl":"https://doi.org/10.1080/17460441.2025.2490253","url":null,"abstract":"Introduction: Knowledge graphs are becoming prominent tools in computational drug discovery. They effectively integrate heterogeneous biomedical data and generate new hypotheses and knowledge.Areas covered: This article is based on a literature review using Google Scholar and PubMed to retrieve articles on existing knowledge graphs relevant to the drug discovery field. The authors compare the types of entities, relationships, and data sources they encompass. Additionally, the authors provide examples of their use in the drug discovery field and discuss potential strategies for advancing this research area.Expert opinion: Knowledge graphs are crucial in drug discovery, but their construction leads to challenges in data integration and consistency. Future research should prioritize the standardization of data sources and data modeling. More efforts are needed for the integration in knowledge graphs of diverse data types, such as chemical structures and epigenetic data, to enhance their effectiveness. Additionally, advancements in large language models should be pursued to aid the development of knowledge graphs, provide intuitive querying capabilities for non-expert users, and explain knowledge graphs -derived predictions, thereby making these tools more accessible and their insights more interpretable for a wider audience.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"20 5","pages":"599-619"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989865","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

Nonhuman primates as valuable models for mpox drug and vaccine discovery. 非人类灵长类动物作为m痘药物和疫苗发现的有价值的模型。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1080/17460441.2025.2489473

Mahmoud E Rashwan, Mohamed A S Amer, Wael M Elshemey, Abdo A Elfiky

{"title":"Nonhuman primates as valuable models for mpox drug and vaccine discovery.","authors":"Mahmoud E Rashwan, Mohamed A S Amer, Wael M Elshemey, Abdo A Elfiky","doi":"10.1080/17460441.2025.2489473","DOIUrl":"10.1080/17460441.2025.2489473","url":null,"abstract":"Introduction: In recent months, monkeypox (mpox) virus (MPXV) infections has grown to be a major worldwide concern. Cynomolgus monkeys, rhesus macaques, marmosets, and baboons are the nonhuman primate (NHP) models that provide the much needed means for developing new therapies against MPXV due to their genetic proximity to humans.Area covered: In this review, the authors discuss epidemiology, transmission, clinical presentation, and the use of NHP in studying the treatment of MPXV over the past two decades on Google Scholar. NHP models have been widely used to evaluate the efficacy of antiviral drugs and antibodies, providing important information regarding immune responses and disease. NHPs continue to be an important mainstay in preclinical testing, enabling the optimization of the efficacy and safety of drugs, antibodies, and vaccines to accelerate the development of effective MPXV treatments for humans.Expert opinion: The intravenous forms of medications like cidofovir, brincidofovir, and Vaccinia Immune Globulin (VIG) constitute the basis of MPXV therapy. Additionally, antibodies such as HAI, PN, and CF assess the efficacy of smallpox vaccination against MPXV in primates. This would help both the development of diagnostic tools and the optimization of vaccine strategies. Moreover, the similarities between MPXV and vaccinia or variola can play a role in developing targeted antiviral treatment methods.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"575-583"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771869","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

Native mass spectrometry for proximity-inducing compounds: a new opportunity for studying chemical-induced protein modulation. 就近诱导化合物的天然质谱分析：研究化学诱导蛋白质调节的新机会。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-03 DOI: 10.1080/17460441.2025.2486146

Emanuele Fabbrizi, Francesco Fiorentino, Fabrizio Casano, Antonello Mai, Dante Rotili

{"title":"Native mass spectrometry for proximity-inducing compounds: a new opportunity for studying chemical-induced protein modulation.","authors":"Emanuele Fabbrizi, Francesco Fiorentino, Fabrizio Casano, Antonello Mai, Dante Rotili","doi":"10.1080/17460441.2025.2486146","DOIUrl":"10.1080/17460441.2025.2486146","url":null,"abstract":"Introduction: Proximity-inducing compounds promote protein-protein interactions by bringing proteins into close spatial alignment. Among them, targeted protein degradation (TPD) compounds are noteworthy for their potential to target previously 'undruggable' proteins. Native mass spectrometry (nMS), a technique that enables the detection of non-covalent interactions, is emerging as a key tool for studying compound-induced ternary complex formation.Areas covered: This review highlights the use of nMS in unraveling the mechanisms of proximity-inducing compounds, focusing on all available studies published since 2020, identified through a PubMed database search. The authors explore how nMS helps investigate the efficacy and mechanisms of proteolysis-targeting chimeras (PROTACs) and molecular glues by capturing the binary and ternary complexes formed by E3 ligases, protein of interest (POI), and these molecules.Expert opinion: nMS excels at analyzing intact protein complexes, providing real-time insights into interactions between E3 ligases, POIs, and proximity-inducing agents. This analysis helps understand the formation, stability, and dynamic nature of the complexes along with precise data on stoichiometry and binding affinities, which are crucial for selecting and refining effective degraders. The future of nMS in TPD research is promising, with potential applications in kinetic analysis, degrader screenings, and exploration of novel E3 ligases and target proteins.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"643-657"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729627","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

Novel drug discovery strategies for chronic obstructive pulmonary disease: the latest developments. 慢性阻塞性肺疾病的新药物发现策略：最新进展。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-14 DOI: 10.1080/17460441.2025.2490251

Luigino Calzetta, Elena Pistocchini, Shima Gholamalishahi, Lucia Grugni, Mario Cazzola, Paola Rogliani

{"title":"Novel drug discovery strategies for chronic obstructive pulmonary disease: the latest developments.","authors":"Luigino Calzetta, Elena Pistocchini, Shima Gholamalishahi, Lucia Grugni, Mario Cazzola, Paola Rogliani","doi":"10.1080/17460441.2025.2490251","DOIUrl":"https://doi.org/10.1080/17460441.2025.2490251","url":null,"abstract":"Introduction: The journey from initial drug discovery to approval for respiratory diseases typically spans approximately 10.4 years and cost over $2.8 billion. This intricate process involves five stages: target identification, therapeutic molecule discovery, preclinical testing, clinical trials, and regulatory approval.Areas covered: This review examines novel drug discovery strategies for chronic obstructive pulmonary disease (COPD), focusing on advanced in vitro models that replicate human lung conditions for accurate drug testing according to the following search string: discovery AND strategy AND COPD. It explores targeted molecular therapies, structure-based drug design, and drug repurposing approaches facilitated by computational analysis. The significance of personalized medicine in tailoring treatments for diverse COPDs is emphasized, highlighting the complexity of the disease and the necessity of these innovative methodologies to improve therapeutic outcomes.Expert opinion: COPD remains a challenging area, with a significant unmet medical need. Despite previous efforts, few effective therapies exist. Innovative in vitro models, targeted molecular therapies, and drug repurposing strategies are showing promise. Emphasizing advanced preclinical models and repurposing existing drugs could transform treatment paradigms, promoting more effective therapies for complex diseases like COPD. These innovations hold potential for enhancing drug discovery efficiency, leading to personalized and precision medicine approaches.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"20 5","pages":"683-692"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005291","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

Recent developments in cystic fibrosis drug discovery: where are we today? 囊性纤维化药物发现的最新进展：我们今天在哪里？

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-05-01 Epub Date: 2025-04-13 DOI: 10.1080/17460441.2025.2490250

Miquéias Lopes-Pacheco, Ashlyn G Winters, JaNise J Jackson, John A Olson, Minsoo Kim, Kaitlyn V Ledwitch, Austin Tedman, Ashish R Jhangiani, Jonathan P Schlebach, Jens Meiler, Lars Plate, Kathryn E Oliver

{"title":"Recent developments in cystic fibrosis drug discovery: where are we today?","authors":"Miquéias Lopes-Pacheco, Ashlyn G Winters, JaNise J Jackson, John A Olson, Minsoo Kim, Kaitlyn V Ledwitch, Austin Tedman, Ashish R Jhangiani, Jonathan P Schlebach, Jens Meiler, Lars Plate, Kathryn E Oliver","doi":"10.1080/17460441.2025.2490250","DOIUrl":"10.1080/17460441.2025.2490250","url":null,"abstract":"Introduction: The advent of variant-specific disease-modifying drugs into clinical practice has provided remarkable benefits for people with cystic fibrosis (PwCF), a multi-organ life-limiting inherited disease. However, further efforts are needed to maximize therapeutic benefits as well as to increase the number of PwCF taking CFTR modulators.Area covered: The authors discuss some of the key limitations of the currently available CFTR modulator therapies (e.g. adverse reactions) and strategies in development to increase the number of available therapeutics for CF. These include novel methods to accelerate theratyping and identification of novel small molecules and cellular targets representing alternative or complementary therapies for CF.Expert opinion: While the CF therapy development pipeline continues to grow, there is a critical need to optimize strategies that will accelerate testing and approval of effective therapies for (ultra)rare CFTR variants as traditional assays and trials are not suitable to address such issues. Another major barrier that needs to be solved is the restricted access to currently available modulator therapies, which remains a significant burden for PwCF who are from racial and ethnic minorities and/or living in underprivileged regions.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"659-682"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810828","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