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

Ultra-high-throughput mass spectrometry in drug discovery: fundamentals and recent advances. 药物发现中的超高通量质谱法：基本原理和最新进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-19 DOI: 10.1080/17460441.2023.2293153

Jon D Williams, Fan Pu, James W Sawicki, Nathaniel L Elsen

{"title":"Ultra-high-throughput mass spectrometry in drug discovery: fundamentals and recent advances.","authors":"Jon D Williams, Fan Pu, James W Sawicki, Nathaniel L Elsen","doi":"10.1080/17460441.2023.2293153","DOIUrl":"10.1080/17460441.2023.2293153","url":null,"abstract":"Introduction: Ultra-high-throughput mass spectrometry, uHT-MS, is a technology that utilizes ionization and sample delivery technologies optimized to enable sampling from well plates at > 1 sample per second. These technologies do not need a chromatographic separation step and can be utilized in a wide variety of assays to detect a broad range of analytes including small molecules, lipids, and proteins.Areas covered: This manuscript provides a brief historical review of high-throughput mass spectrometry and the recently developed technologies that have enabled uHT-MS. The report also provides examples and references on how uHT-MS has been used in biochemical and chemical assays, nuisance compound profiling, protein analysis and high throughput experimentation for chemical synthesis.Expert opinion: The fast analysis time provided by uHT-MS is transforming how biochemical and chemical assays are performed in drug discovery. The potential to associate phenotypic responses produced by 1000's of compound treatments with changes in endogenous metabolite and lipid signals is becoming feasible. With the augmentation of simple, fast, high-throughput sample preparation, the scope of uHT-MS usage will increase. However, it likely will not supplant LC-MS for analyses that require low detection limits from complex matrices or characterization of complex biotherapeutics such as antibody-drug conjugates.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794801","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 is the future of click chemistry in drug discovery and development? 点击化学在药物研发中的前景如何？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2024-01-12 DOI: 10.1080/17460441.2024.2302151

Ana C Amorim, Anthony J Burke

{"title":"What is the future of click chemistry in drug discovery and development?","authors":"Ana C Amorim, Anthony J Burke","doi":"10.1080/17460441.2024.2302151","DOIUrl":"10.1080/17460441.2024.2302151","url":null,"abstract":"Introduction: The concept of click chemistry was introduced in 2001 as an effective, efficient, and sustainable approach to making functional groups harnessing the thermodynamic properties of a set of known chemical reactions that are based on nature. Some of the most common examples include reactions that produce 1,2,3-triazoles, which have been used with great success in drug discovery and development, and in chemical biology. The reactions unite two molecules quickly and irreversibly, and the reactions can be performed inside living cells, without harming the cell.Areas covered: The main focus of this perspective is the future of click chemistry in drug discovery and development, exemplified by novel click chemistry approaches and other aspects of the drug development enterprise, like SPAAC and analogous techniques, PROTACs, as well as diversity-oriented click chemistry.Expert opinion: Drug discovery and development has benefited enormously from the amazing advances that have been made in the field of click chemistry since 2001. The methods most likely to have the most future applications include metal-catalyzed azide-alkyne cycloadditions giving 1,2,3-triazoles, SPAAC for medical diagnostics and vaccine development, other congeners, Sulfur-Fluoride Exchange (SuFEx) and Diversity-Oriented Clicking (DOC), a concept with diverse molecular methodology with the potential for obtaining extensive molecular diversity.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424542","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

Advances in ion channel high throughput screening: where are we in 2023? 离子通道高通量筛选的进展：2023 年我们在哪里？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-18 DOI: 10.1080/17460441.2023.2294948

Mark L Dallas, Damian Bell

{"title":"Advances in ion channel high throughput screening: where are we in 2023?","authors":"Mark L Dallas, Damian Bell","doi":"10.1080/17460441.2023.2294948","DOIUrl":"10.1080/17460441.2023.2294948","url":null,"abstract":"Introduction: Automated Patch Clamp (APC) technology has become an integral element in ion channel research, drug discovery and development pipelines to overcome the use of the highly time-consuming manual patch clamp (MPC) procedures. This automated technology offers increased throughput and promises a new model in obtaining ion channel recordings, which has significant relevance to the development of novel therapies and safety profiling of candidate therapeutic compounds.Areas covered: This article reviews the recent innovations in APC technology, including platforms, and highlights how they have facilitated usage in both industry and academia. The review also provides an overview of the ion channel research endeavors and how APC platforms have contributed to the understanding of ion channel research, pharmacological tools and therapeutics. Furthermore, the authors provide their opinion on the challenges and goals for APC technology going forward to accelerate academic research and drug discovery across a host of therapeutic areas.Expert opinion: It is clear that APC technology has progressed drug discovery programs, specifically in the field of neuroscience and cardiovascular research. The challenge for the future is to keep pace with fundamental research and improve translation of the large datasets obtained.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794516","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 SH-SY5Y cell line: a valuable tool for Parkinson's disease drug discovery. SH-SY5Y 细胞系：发现帕金森病药物的重要工具。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-19 DOI: 10.1080/17460441.2023.2293158

Manisha Pandey, Varnita Karmakar, Ankit Majie, Monika Dwivedi, Shadab Md, Bapi Gorain

{"title":"The SH-SY5Y cell line: a valuable tool for Parkinson's disease drug discovery.","authors":"Manisha Pandey, Varnita Karmakar, Ankit Majie, Monika Dwivedi, Shadab Md, Bapi Gorain","doi":"10.1080/17460441.2023.2293158","DOIUrl":"10.1080/17460441.2023.2293158","url":null,"abstract":"Introduction: Owing to limited efficient treatment strategies for highly prevalent and distressing Parkinson's disease (PD), an impending need emerged for deciphering new modes and mechanisms for effective management. SH-SY5Y-based in vitro neuronal models have emerged as a new possibility for the elucidation of cellular and molecular processes in the pathogenesis of PD. SH-SY5Y cells are of human origin, adhered to catecholaminergic neuronal attributes, which consequences in imparting wide acceptance and significance to this model over conventional in vitro PD models for high-throughput screening of therapeutics.Areas covered: Herein, the authors review the SH-SY5Y cell line and its value to PD research. The authors also provide the reader with their expert perspectives on how these developments can lead to the development of new impactful therapeutics.Expert opinion: Encouraged by recent research on SH-SY5Y cell lines, it was envisaged that this in vitro model can serve as a primary model for assessing efficacy and toxicity of new therapeutics as well as for nanocarriers' capacity in delivering therapeutic agents across BBB. Considering the proximity with human neuronal environment as in pathogenic PD conditions, SH-SY5Y cell lines vindicated consistency and reproducibility in experimental results. Accordingly, exploitation of this standardized SH-SY5Y cell line can fast-track the drug discovery and development path for novel therapeutics.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794687","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

Designing drugs optimized for both blood-brain barrier permeation and intra-cerebral partition. 设计同时具有血脑屏障渗透性和脑内分配性的最佳药物。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-25 DOI: 10.1080/17460441.2023.2294118

Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata

{"title":"Designing drugs optimized for both blood-brain barrier permeation and intra-cerebral partition.","authors":"Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata","doi":"10.1080/17460441.2023.2294118","DOIUrl":"10.1080/17460441.2023.2294118","url":null,"abstract":"Introduction: With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS.Areas covered: This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed.Expert opinion: Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032216","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

Advances in structure-activity relationships of HDAC inhibitors as HIV latency-reversing agents. 作为艾滋病潜伏期逆转剂的 HDAC 抑制剂的结构-活性关系研究进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2024-01-23 DOI: 10.1080/17460441.2024.2305730

Samima Khatun, Sk Abdul Amin, Debasmita Choudhury, Boby Chowdhury, Tarun Jha, Shovanlal Gayen

{"title":"Advances in structure-activity relationships of HDAC inhibitors as HIV latency-reversing agents.","authors":"Samima Khatun, Sk Abdul Amin, Debasmita Choudhury, Boby Chowdhury, Tarun Jha, Shovanlal Gayen","doi":"10.1080/17460441.2024.2305730","DOIUrl":"10.1080/17460441.2024.2305730","url":null,"abstract":"Introduction: HIV-infected cells may rebound due to the existence of the silent HIV-infected memory CD4+ T cells (HIV latency). This HIV latency makes the disease almost incurable. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). Hence, inhibition of HDAC is considered a prime target for HIV latency reversal.Areas covered: A brief biology and function of HDACs have been discussed to identify key points to design HDAC inhibitors (HDACis). This article summarizes recent achievements in the development of HDACis to achieve HIV latency reversal. Structure-activity relationships (SARs) of some series of compounds were also explored.Expert opinion: Depletion of the HIV reservoir is the only way to end this deadly epidemic. HDACis are latency-reversing agents (LRA) that can be used to 'shock' the latently infected CD4+ T cells to induce them to produce viral proteins. It is interesting to note that HDAC3, which is extensively expressed in resting T cells, is specifically preferred by benzamide-containing HDACis for inhibition. Thus, the benzamide class of compounds should be explored. Nevertheless, more data on selective HDAC inhibition is needed for further development of HDACis in HIV latency reversal.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519981","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

Vascular organs-on-chip made with patient-derived endothelial cells: technologies to transform drug discovery and disease modeling. 利用源自患者的内皮细胞制造芯片上的血管器官：改变药物发现和疾病建模的技术。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-20 DOI: 10.1080/17460441.2023.2294947

Chloe P Whitworth, William J Polacheck

{"title":"Vascular organs-on-chip made with patient-derived endothelial cells: technologies to transform drug discovery and disease modeling.","authors":"Chloe P Whitworth, William J Polacheck","doi":"10.1080/17460441.2023.2294947","DOIUrl":"10.1080/17460441.2023.2294947","url":null,"abstract":"Introduction: Vascular diseases impart a tremendous burden on healthcare systems in the United States and across the world. Efforts to improve therapeutic interventions are hindered by limitations of current experimental models. The integration of patient-derived cells with organ-on-chip (OoC) technology is a promising avenue for preclinical drug screening that improves upon traditional cell culture and animal models.Areas covered: The authors review induced pluripotent stem cells (iPSC) and blood outgrowth endothelial cells (BOEC) as two sources for patient-derived endothelial cells (EC). They summarize several studies that leverage patient-derived EC and OoC for precision disease modeling of the vasculature, with a focus on applications for drug discovery. They also highlight the utility of patient-derived EC in other translational endeavors, including ex vivo organogenesis and multi-organ-chip integration.Expert opinion: Precision disease modeling continues to mature in the academic space, but end-use by pharmaceutical companies is currently limited. To fully realize their transformative potential, OoC systems must balance their complexity with their ability to integrate with the highly standardized and high-throughput experimentation required for drug discovery and development.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794891","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

Will the hype of automated drug discovery finally be realized? 自动药物发现的热潮最终会实现吗？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-11 DOI: 10.1080/17460441.2023.2293157

Wenqiang Cui, Shuguang Yuan

引用次数: 0

Have spirocyclic scaffolds been properly utilized in recent drug discovery efforts? 螺旋环支架在最近的药物发现工作中是否得到了适当利用？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2024-01-18 DOI: 10.1080/17460441.2024.2305735

Erica Benedetti, Laurent Micouin

引用次数: 0

The vinyl sulfone motif as a structural unit for novel drug design and discovery. 乙烯基砜基序作为新型药物设计和发现的结构单元。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2284201

You-Cai Xiao, Fen-Er Chen

{"title":"The vinyl sulfone motif as a structural unit for novel drug design and discovery.","authors":"You-Cai Xiao, Fen-Er Chen","doi":"10.1080/17460441.2023.2284201","DOIUrl":"10.1080/17460441.2023.2284201","url":null,"abstract":"Introduction: Vinyl sulfones are a special sulfur-containing structural unit that have attracted considerable attention, owing to their important role in serving as key structural motifs of various biologically active compounds as well as serving as versatile building blocks for organic transformations. The synthetic strategy of vinyl sulfone derivatives has been substantially upgraded over the past 30 years, and the wide application of this functional group in drug design and discovery has been promoted.Area covered: In this review, the authors review the application of vinyl sulfones in drug discovery and select optimized compounds which might have significant impact or potential inspiration for drug design.Expert opinion: Vinyl sulfones have been reported to target various macromolecular targets via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, and so on. Thus, it has been significantly applied as a privileged scaffold in the design of anticancer, anti-infective, anti-inflammatory, and neuroprotective agents. However, much work remains to be done to improve the drug-like properties, such as chemical and metabolic stability, ADME, and toxicity. Besides, the chemical space of vinyl sulfones needs to be expanded, including but not limited to the design of constrained endocyclic and exocyclic vinyl sulfones.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397117","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