Expert Opinion on Drug Discovery最新文献_第10页

Calcium channel blockers' contribution to overcoming Current drug discovery challenges in Alzheimer's disease. 钙通道阻滞剂对克服当前阿尔茨海默病药物发现挑战的贡献。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2266994

Paul J Bernard, Djamila Bellili, Lhassane Ismaili

{"title":"Calcium channel blockers' contribution to overcoming Current drug discovery challenges in Alzheimer's disease.","authors":"Paul J Bernard, Djamila Bellili, Lhassane Ismaili","doi":"10.1080/17460441.2023.2266994","DOIUrl":"10.1080/17460441.2023.2266994","url":null,"abstract":"Introduction: Alzheimer's disease (AD) is a progressive, irreversible, and multifactorial brain disorder that gradually and insidiously destroys individual's memory, thinking, and other cognitive abilities.Areas covered: In this perspective, the authors examine the complex and multifactorial nature of Alzheimer's disease and believe that the best approach to develop new drugs is the MTDL strategy, which obviously faces several challenges. These challenges include identifying the key combination of targets and their suitability for coordinated actions, as well as developing an acceptable pharmacokinetic and toxicological profile to deliver a drug candidate.Expert opinion: Since calcium plays a crucial role in the pathology of AD, a polypharmacological approach with calcium channel blockers reinforced by activities targeting other factors involved in AD is a serious option in our opinion. This is exemplified by a phase III clinical trial using a drug combination approach with Losartan, Amlodipine (a calcium channel blocker), and Atorvastatin, as well as several MTDL-based calcium channel blockade approaches with a promising in vitro and in vivo profile.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107881","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

Current advances in the use of bioluminescence assays for drug discovery: an update of the last ten years. 生物发光分析用于药物发现的最新进展：过去十年的更新。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2266989

Maria Maddalena Calabretta, Elisa Michelini

{"title":"Current advances in the use of bioluminescence assays for drug discovery: an update of the last ten years.","authors":"Maria Maddalena Calabretta, Elisa Michelini","doi":"10.1080/17460441.2023.2266989","DOIUrl":"10.1080/17460441.2023.2266989","url":null,"abstract":"Introduction: Bioluminescence is a well-established optical detection technique widely used in several bioanalytical applications, including high-throughput and high-content screenings. Thanks to advances in synthetic biology techniques and deep learning, a wide portfolio of luciferases is now available with tuned emission wavelengths, kinetics, and high stability. These luciferases can be implemented in the drug discovery and development pipeline, allowing high sensitivity and multiplexing capability.Areas covered: This review summarizes the latest advancements of bioluminescent systems as toolsets in drug discovery programs for in vitro applications. Particular attention is paid to the most advanced bioluminescence-based technologies for drug screening over the past 10 years (from 2013 to 2023) such as cell-free assays, cell-based assays based on genetically modified cells, bioluminescence resonance energy transfer, and protein complementation assays in 2D and 3D cell models.Expert opinion: The availability of tuned bioluminescent proteins with improved emission and stability properties is vital for the development of bioluminescence assays for drug discovery, spanning from reporter gene technology to protein-protein techniques. Further studies, combining machine learning with synthetic biology, will be necessary to obtain new tools for sustainable and highly predictive bioluminescent drug discovery platforms.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182389","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

γ-Secretase: once and future drug target for Alzheimer's disease. γ-分泌酶：阿尔茨海默病的曾经和未来的药物靶点。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2277350

Michael S Wolfe

引用次数: 0

Leveraging nitrogen occurrence in approved drugs to identify structural patterns. 利用已批准药物中氮的存在来识别结构模式。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2266990

Vijay H Masand, Sami Al-Hussain, Abdullah Y Alzahrani, Nahed N E El-Sayed, Chien Ing Yeo, Yee Seng Tan, Magdi E A Zaki

{"title":"Leveraging nitrogen occurrence in approved drugs to identify structural patterns.","authors":"Vijay H Masand, Sami Al-Hussain, Abdullah Y Alzahrani, Nahed N E El-Sayed, Chien Ing Yeo, Yee Seng Tan, Magdi E A Zaki","doi":"10.1080/17460441.2023.2266990","DOIUrl":"10.1080/17460441.2023.2266990","url":null,"abstract":"Background: The process of drug development and discovery is costly and slow. Although an understanding of molecular design principles and biochemical processes has progressed, it is essential to minimize synthesis-testing cycles. An effective approach is to analyze key heteroatoms, including oxygen and nitrogen. Herein, we present an analysis focusing on the utilization of nitrogen atoms in approved drugs.Research design and methods: The present work examines the frequency, distribution, prevalence, and diversity of nitrogen atoms in a dataset comprising 2,049 small molecules approved by different regulatory agencies (FDA and others). Various types of nitrogen atoms, such as sp3-, sp2-, sp-hybridized, planar, ring, and non-ring are included in this investigation.Results: The results unveil both previously reported and newly discovered patterns of nitrogen atom distribution around the center of mass in the majority of drug molecules.Conclusions: This study has highlighted intriguing trends in the role of nitrogen atoms in drug design and development. The majority of drugs contain 1-3 nitrogen atoms within 5Å from the center of mass (COM) of a molecule, with a higher preference for the ring and planar nitrogen atoms. The results offer invaluable guidance for the multiparameter optimization process, thus significantly contributing toward the conversion of lead compounds into potential drug candidates.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41137731","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 the preclinical discovery and development of ensitrelvir as a COVID-19 therapeutic option. 从恩司他韦作为新冠肺炎治疗选择的临床前发现和开发中吸取的经验教训。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2267001

Sara Ferraro, Irma Convertino, Emiliano Cappello, Giulia Valdiserra, Marco Bonaso, Marco Tuccori

{"title":"Lessons learnt from the preclinical discovery and development of ensitrelvir as a COVID-19 therapeutic option.","authors":"Sara Ferraro, Irma Convertino, Emiliano Cappello, Giulia Valdiserra, Marco Bonaso, Marco Tuccori","doi":"10.1080/17460441.2023.2267001","DOIUrl":"10.1080/17460441.2023.2267001","url":null,"abstract":"Introduction: The COVID-19 pandemic stimulated the development of several therapeutic tools with several degrees of success. Ensitrelvir, a protease inhibitor that blocks the replication of SARS-CoV-2, can reduce the viral load and the severity of symptoms in infected patients and become available for emergency use in Japan. Clinical trials showed a good tolerability profile although the potential for interactions with substrates, inhibitors, and inducers of CYP3A must be considered. The occurrence of resistance is also a matter of investigation.Areas covered: In this article, the authors describe the development of ensitrelvir starting from the identification of the molecule to the pre-clinical and clinical trials up to the post-authorization phase.Expert opinion: Ensitrelvir was developed in a late phase of the pandemic when the availability of patients that can be candidate to enter the clinical trial was limited with consequences for the possibility of assessing certain outcomes and for the robustness of results. Although the evidence about the benefits of ensitrelvir in COVID-19 is not questionable, the problems of interactions with other drugs, emerging resistant variants, the availability of alternative therapeutic options, costs, and accessibility will concur to its probable limited clinical use in the future.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41196144","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 vitro screening technologies for the discovery and development of novel drugs against Toxoplasma gondii. 用于发现和开发抗弓形虫新药的体外筛选技术。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2276349

Joachim Müller, Andrew Hemphill

{"title":"In vitro screening technologies for the discovery and development of novel drugs against Toxoplasma gondii.","authors":"Joachim Müller, Andrew Hemphill","doi":"10.1080/17460441.2023.2276349","DOIUrl":"10.1080/17460441.2023.2276349","url":null,"abstract":"Introduction: Toxoplasmosis constitutes a challenge for public health, animal production and welfare. Since more than 60 years, only a limited panel of drugs has been in use for clinical applications.Areas covered: Herein, the authors describe the methodology and the results of library screening approaches to identify inhibitors of Toxoplasma gondii and related strains. The authors then provide the reader with their expert perspectives for the future.Expert opinion: Various library screening projects, in particular those using reporter strains, have led to the identification of numerous compounds with good efficacy and specificity in vitro. However, only few compounds are effective in suitable animal models such as rodents. Whereas no novel compound has cleared the hurdle to applications in humans, the few compounds with known indication and application profiles in human patients are of interest for further investigations. Taken together, drug repurposing as well as high-throughput screening of novel compound libraries may shorten the way to novel drugs against toxoplasmosis.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71422172","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 application of WaterMap-guided structure-based virtual screening in novel drug discovery. 基于WaterMap引导结构的虚拟筛选在新药发现中的应用。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2267015

Agnieszka A Kaczor, Agata Zięba, Dariusz Matosiuk

{"title":"The application of WaterMap-guided structure-based virtual screening in novel drug discovery.","authors":"Agnieszka A Kaczor, Agata Zięba, Dariusz Matosiuk","doi":"10.1080/17460441.2023.2267015","DOIUrl":"10.1080/17460441.2023.2267015","url":null,"abstract":"Introduction: Nowadays, it is widely accepted that water molecules play a key role in binding a ligand to a molecular target. Neglecting water molecules in the process of molecular recognition was the result of several failures of the structure-based drug discovery campaigns. The application of WaterMap, in particular WaterMap-guided molecular docking, enables the reasonably accurate and quick description of the location and energetics of water molecules at the ligand-protein interface.Areas covered: In this review, the authors shortly discuss the importance of water in drug design and discovery and provide a brief overview of the computational approaches used to predict the solvent-related effects for the purposes of presenting WaterMap in the context of other available techniques and tools. A concise description of WaterMap concept is followed by the presentation of WaterMap-assisted virtual screening literature published between 2013 and 2023.Expert opinion: In recent years, WaterMap software has been extensively used to support structure-based drug design, in particular structure-based virtual screening. Indeed, it is a useful tool to rescore docking results considering water molecules in the binding pocket. Although WaterMap allows for the consideration of the dynamic behavior of water molecules in the binding site, for best accuracy, its application in conjunction with other techniques such as molecular mechanics-generalized Born surface area of FEP (Free Energy Perturbation) is recommended.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107088","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

Drugs targeting the particle for arrangement of quaternary structure (PAQosome) and protein complex assembly. 靶向颗粒的药物用于排列四元结构（PAQosome）和蛋白质复合物组装。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/17460441.2023.2267974

Maxime Pinard, Asmae Moursli, Benoit Coulombe

{"title":"Drugs targeting the particle for arrangement of quaternary structure (PAQosome) and protein complex assembly.","authors":"Maxime Pinard, Asmae Moursli, Benoit Coulombe","doi":"10.1080/17460441.2023.2267974","DOIUrl":"10.1080/17460441.2023.2267974","url":null,"abstract":"Introduction: The PAQosome is a 12-subunit complex that acts as a co-factor of the molecular chaperones HSP90 and HSP70. This co-chaperone has been shown to participate in assembly and maturation of several protein complexes, including nuclear RNA polymerases, RNA processing factors, the ribosome, PIKKs, and others. Subunits of the PAQosome, adaptors, and clients have been reported to be involved in various diseases, making them interesting targets for drug discovery.Area covered: In this review, the authors cover the detailed mechanisms of PAQosome and chaperone function. Specifically, the authors summarize the status of the PAQosome and some related chaperones and co-chaperones as candidate targets for drug discovery. Indeed, a number of compounds are currently being tested for the development of treatments against diseases, such as cancers and neurodegenerative conditions.Expert opinion: Searching for new drugs targeting the PAQosome requires a better understanding of PAQosome subunit interactions and the discovery of new interaction partners. Thus, PAQosome subunit crystallization is an important experiment to initiate virtual screening against new target and the development of in silico tools such as AlphaFold-multimer could accelerate the search for new interaction partner and determine more rapidly the interaction pocket needed for virtual drug screening.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233725","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

Perspectives on the success of plasma lipidomics in cardiovascular drug discovery and future challenges 血浆脂质组学在心血管药物研发中的成功经验与未来挑战

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2023-12-12 DOI: 10.1080/17460441.2023.2292039

Timothy Abrahams, Stephen J. Nicholls

引用次数: 0

Bacterial synthetic biology: tools for novel drug discovery. 细菌合成生物学：新药发现工具。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2023-07-01 Epub Date: 2023-07-23 DOI: 10.1080/17460441.2023.2239704

Xiyan Wang, Nan Zhou, Baojun Wang

{"title":"Bacterial synthetic biology: tools for novel drug discovery.","authors":"Xiyan Wang, Nan Zhou, Baojun Wang","doi":"10.1080/17460441.2023.2239704","DOIUrl":"10.1080/17460441.2023.2239704","url":null,"abstract":"Introduction: Bacterial synthetic biology has provided powerful tools to revolutionize the drug discovery process. These tools can be harnessed to generate bacterial novel pharmaceutical compounds with enhanced bioactivity and selectivity or to create genetically modified microorganisms as living drugs.Areas covered: This review provides a current overview of the state-of-the-art in bacterial synthetic biology tools for novel drug discovery. The authors discuss the application of these tools including bioinformatic tools, CRISPR tools, engineered bacterial transcriptional regulators, and synthetic biosensors for novel drug discovery. Additionally, the authors present the recent progress on reprogramming bacteriophages as living drugs to fight against antibiotic-resistant pathogens.Expert opinion: The field of using bacterial synthetic biology tools for drug discovery is rapidly advancing. However, challenges remain in developing reliable and robust methods to engineer bacteria. Further advancements in synthetic biology hold promise to speed up drug discovery, facilitating the development of novel therapeutics against various diseases.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858741","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