Expert Opinion on Drug Discovery最新文献_第9页

Identification of the abnormalities in astrocytic functions as potential drug targets for neurodegenerative disease. 将星形胶质细胞功能异常确定为治疗神经退行性疾病的潜在药物靶点。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-05-01 Epub Date: 2024-02-26 DOI: 10.1080/17460441.2024.2322988

Valtteri Syvänen, Jari Koistinaho, Šárka Lehtonen

{"title":"Identification of the abnormalities in astrocytic functions as potential drug targets for neurodegenerative disease.","authors":"Valtteri Syvänen, Jari Koistinaho, Šárka Lehtonen","doi":"10.1080/17460441.2024.2322988","DOIUrl":"10.1080/17460441.2024.2322988","url":null,"abstract":"Introduction: Historically, astrocytes were seen primarily as a supportive cell population within the brain; with neurodegenerative disease research focusing exclusively on malfunctioning neurons. However, astrocytes perform numerous tasks that are essential for maintenance of the central nervous system`s complex processes. Disruption of these functions can have negative consequences; hence, it is unsurprising to observe a growing amount of evidence for the essential role of astrocytes in the development and progression of neurodegenerative diseases. Targeting astrocytic functions may serve as a potential disease-modifying drug therapy in the future.Areas covered: The present review emphasizes the key astrocytic functions associated with neurodegenerative diseases and explores the possibility of pharmaceutical interventions to modify these processes. In addition, the authors provide an overview of current advancement in this field by including studies of possible drug candidates.Expert opinion: Glial research has experienced a significant renaissance in the last quarter-century. Understanding how disease pathologies modify or are caused by astrocyte functions is crucial when developing treatments for brain diseases. Future research will focus on building advanced models that can more precisely correlate to the state in the human brain, with the goal of routinely testing therapies in these models.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"603-616"},"PeriodicalIF":6.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971487","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

C. elegans: a prominent platform for modeling and drug screening in neurological disorders. elegans: 神经系统疾病建模和药物筛选的重要平台。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-05-01 Epub Date: 2024-03-20 DOI: 10.1080/17460441.2024.2329103

Stefano Romussi, Sebastián Giunti, Natalia Andersen, María José De Rosa

{"title":"C. elegans: a prominent platform for modeling and drug screening in neurological disorders.","authors":"Stefano Romussi, Sebastián Giunti, Natalia Andersen, María José De Rosa","doi":"10.1080/17460441.2024.2329103","DOIUrl":"10.1080/17460441.2024.2329103","url":null,"abstract":"Introduction: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience.Areas covered: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states.Expert opinion: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"565-585"},"PeriodicalIF":6.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174135","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 learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer’s disease 从索拉尼珠单抗作为阿尔茨海默病前瞻性治疗策略的失败中汲取教训

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-29 DOI: 10.1080/17460441.2024.2348142

Madia Lozupone, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Francesco Panza

引用次数: 0

Treatment of highly virulent mammarenavirus infections—status quo and future directions 高致病性猛玛病毒感染的治疗--现状与未来方向

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-12 DOI: 10.1080/17460441.2024.2340494

Ivette A. Nuñez, Anya Crane, Ian Crozier, Gabriella Worwa, Jens H. Kuhn

引用次数: 0

Omega-3 polyunsaturated fatty acid derived lipid mediators: a comprehensive update on their application in anti-cancer drug discovery 欧米伽-3 多不饱和脂肪酸衍生脂质介质：抗癌药物研发应用的全面更新

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-09 DOI: 10.1080/17460441.2024.2340493

Michael Murray

引用次数: 0

Potential Alzheimer’s disease drug targets identified through microglial biology research 通过小胶质细胞生物学研究确定阿尔茨海默病潜在药物靶点

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-08 DOI: 10.1080/17460441.2024.2335210

Izabela Lepiarz-Raba, Taufik Hidayat, Anthony J. Hannan, Ali Jawaid

引用次数: 0

The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma. 用于治疗多发性骨髓瘤的 ciltacabtagene autoleucel（Cilta-cel）的临床前发现和临床开发。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-01 Epub Date: 2024-02-18 DOI: 10.1080/17460441.2024.2319672

Irene Strassl, Klaus Podar

{"title":"The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma.","authors":"Irene Strassl, Klaus Podar","doi":"10.1080/17460441.2024.2319672","DOIUrl":"10.1080/17460441.2024.2319672","url":null,"abstract":"Introduction: Despite remarkable therapeutic advances over the last two decades, which have resulted in dramatic improvements in patient survival, multiple myeloma (MM) is still considered an incurable disease. Therefore, there is a high need for new treatment strategies. Genetically engineered/redirected chimeric antigen receptor (CAR) T cells may represent the most compelling modality of immunotherapy for cancer treatment in general, and MM in particular. Indeed, unprecedented response rates have led to the recent approvals of the first two BCMA-targeted CAR T cell products idecabtagene-vicleucel ('Ide-cel') and ciltacabtagene-autoleucel ('Cilta-Cel') for the treatment of heavily pretreated MM patients. In addition, both are emerging as a new standard-of-care also in earlier lines of therapy.Areas covered: This article briefly reviews the history of the preclinical development of CAR T cells, with a particular focus on Cilta-cel. Moreover, it summarizes the newest clinical data on Cilta-cel and discusses strategies to further improve its activity and reduce its toxicity.Expert opinion: Modern next-generation immunotherapy is continuously transforming the MM treatment landscape. Despite several caveats of CAR T cell therapy, including its toxicity, costs, and limited access, prolonged disease-free survival and potential cure of MM are finally within reach.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"377-391"},"PeriodicalIF":6.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899609","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 applications of artificial intelligence in RNA-targeted small molecule drug discovery. 人工智能在 RNA 靶向小分子药物发现中的最新应用。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-01 Epub Date: 2024-02-06 DOI: 10.1080/17460441.2024.2313455

Ella Czarina Morishita, Shingo Nakamura

{"title":"Recent applications of artificial intelligence in RNA-targeted small molecule drug discovery.","authors":"Ella Czarina Morishita, Shingo Nakamura","doi":"10.1080/17460441.2024.2313455","DOIUrl":"10.1080/17460441.2024.2313455","url":null,"abstract":"Introduction: Targeting RNAs with small molecules offers an alternative to the conventional protein-targeted drug discovery and can potentially address unmet and emerging medical needs. The recent rise of interest in the strategy has already resulted in large amounts of data on disease associated RNAs, as well as on small molecules that bind to such RNAs. Artificial intelligence (AI) approaches, including machine learning and deep learning, present an opportunity to speed up the discovery of RNA-targeted small molecules by improving decision-making efficiency and quality.Areas covered: The topics described in this review include the recent applications of AI in the identification of RNA targets, RNA structure determination, screening of chemical compound libraries, and hit-to-lead optimization. The impact and limitations of the recent AI applications are discussed, along with an outlook on the possible applications of next-generation AI tools for the discovery of novel RNA-targeted small molecule drugs.Expert opinion: Key areas for improvement include developing AI tools for understanding RNA dynamics and RNA - small molecule interactions. High-quality and comprehensive data still need to be generated especially on the biological activity of small molecules that target RNAs.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"415-431"},"PeriodicalIF":6.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697200","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 drug design strategies for discovering novel tuberculosis therapeutics. 发现新型结核病疗法的硅学药物设计策略。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-01 Epub Date: 2024-02-19 DOI: 10.1080/17460441.2024.2319042

Christian S Carnero Canales, Aline Renata Pavan, Jean Leandro Dos Santos, Fernando Rogério Pavan

{"title":"In silico drug design strategies for discovering novel tuberculosis therapeutics.","authors":"Christian S Carnero Canales, Aline Renata Pavan, Jean Leandro Dos Santos, Fernando Rogério Pavan","doi":"10.1080/17460441.2024.2319042","DOIUrl":"10.1080/17460441.2024.2319042","url":null,"abstract":"Introduction: Tuberculosis remains a significant concern in global public health due to its intricate biology and propensity for developing antibiotic resistance. Discovering new drugs is a protracted and expensive endeavor, often spanning over a decade and incurring costs in the billions. However, computer-aided drug design (CADD) has surfaced as a nimbler and more cost-effective alternative. CADD tools enable us to decipher the interactions between therapeutic targets and novel drugs, making them invaluable in the quest for new tuberculosis treatments.Areas covered: In this review, the authors explore recent advancements in tuberculosis drug discovery enabled by in silico tools. The main objectives of this review article are to highlight emerging drug candidates identified through in silico methods and to provide an update on the therapeutic targets associated with Mycobacterium tuberculosis.Expert opinion: These in silico methods have not only streamlined the drug discovery process but also opened up new horizons for finding novel drug candidates and repositioning existing ones. The continued advancements in these fields hold great promise for more efficient, ethical, and successful drug development in the future.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"471-491"},"PeriodicalIF":6.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905375","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

Chemoinformatic approaches for navigating large chemical spaces. 浏览大型化学空间的化学信息学方法。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-04-01 Epub Date: 2024-02-05 DOI: 10.1080/17460441.2024.2313475

Martin Vogt

{"title":"Chemoinformatic approaches for navigating large chemical spaces.","authors":"Martin Vogt","doi":"10.1080/17460441.2024.2313475","DOIUrl":"10.1080/17460441.2024.2313475","url":null,"abstract":"Introduction: Large chemical spaces (CSs) include traditional large compound collections, combinatorial libraries covering billions to trillions of molecules, DNA-encoded chemical libraries comprising complete combinatorial CSs in a single mixture, and virtual CSs explored by generative models. The diverse nature of these types of CSs require different chemoinformatic approaches for navigation.Areas covered: An overview of different types of large CSs is provided. Molecular representations and similarity metrics suitable for large CS exploration are discussed. A summary of navigation of CSs in generative models is provided. Methods for characterizing and comparing CSs are discussed.Expert opinion: The size of large CSs might restrict navigation to specialized algorithms and limit it to considering neighborhoods of structurally similar molecules. Efficient navigation of large CSs not only requires methods that scale with size but also requires smart approaches that focus on better but not necessarily larger molecule selections. Deep generative models aim to provide such approaches by implicitly learning features relevant for targeted biological properties. It is unclear whether these models can fulfill this ideal as validation is difficult as long as the covered CSs remain mainly virtual without experimental verification.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"403-414"},"PeriodicalIF":6.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650636","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