Drug Discovery Today: Technologies最新文献

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Data-independent acquisition (DIA): An emerging proteomics technology for analysis of drug-metabolizing enzymes and transporters 数据独立获取(DIA):一种新兴的蛋白质组学技术,用于分析药物代谢酶和转运蛋白
Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.06.006
Jiapeng Li, Logan S. Smith, Hao-Jie Zhu
{"title":"Data-independent acquisition (DIA): An emerging proteomics technology for analysis of drug-metabolizing enzymes and transporters","authors":"Jiapeng Li,&nbsp;Logan S. Smith,&nbsp;Hao-Jie Zhu","doi":"10.1016/j.ddtec.2021.06.006","DOIUrl":"10.1016/j.ddtec.2021.06.006","url":null,"abstract":"<div><p>Data-independent acquisition (DIA) proteomics<span> is a recently-developed global mass spectrometry (MS)-based proteomics strategy. In a DIA method, precursor ions are isolated into pre-defined isolation windows and fragmented; all fragmented ions in each window are then analyzed by a high-resolution mass spectrometer. DIA proteomics analysis is characterized by a broad protein coverage, high reproducibility, and accuracy, and its combination with advances in other techniques such as sample preparation and computational data analysis could lead to further improvements in assay performances. DIA technology has been increasingly utilized in various proteomics studies, including quantifying drug-metabolizing enzymes<span><span> and transporters. Quantitative proteomics<span> study of drug-metabolizing enzymes and transporters could lead to a better understanding of pharmacokinetics and </span></span>pharmacodynamics<span> and facilitate drug development. This review summarizes the application of DIA technology in proteomic analysis of drug-metabolizing enzymes and transporters.</span></span></span></p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2021.06.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39587150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Development of biotherapeutics and biosimilars 生物治疗药物和生物仿制药的发展
Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.10.006
Zoltán Urbányi
{"title":"Development of biotherapeutics and biosimilars","authors":"Zoltán Urbányi","doi":"10.1016/j.ddtec.2021.10.006","DOIUrl":"10.1016/j.ddtec.2021.10.006","url":null,"abstract":"","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39732460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From computer-aided drug discovery to computer-driven drug discovery 从计算机辅助药物发现到计算机驱动药物发现
Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.08.001
Leah Frye, Sathesh Bhat, Karen Akinsanya, Robert Abel
{"title":"From computer-aided drug discovery to computer-driven drug discovery","authors":"Leah Frye,&nbsp;Sathesh Bhat,&nbsp;Karen Akinsanya,&nbsp;Robert Abel","doi":"10.1016/j.ddtec.2021.08.001","DOIUrl":"10.1016/j.ddtec.2021.08.001","url":null,"abstract":"<div><p><span>Computational chemistry and structure-based design have traditionally been viewed as a subset of tools that could aid acceleration of the drug discovery<span> process, but were not commonly regarded as a driving force in small molecule drug discovery. In the last decade however, there have been dramatic advances in the field, including (1) development of physics-based computational approaches to accurately predict a broad variety of endpoints from potency to solubility, (2) improvements in artificial intelligence and deep learning methods and (3) dramatic increases in computational power with the advent of GPUs and cloud computing, resulting in the ability to explore and accurately profile vast amounts of drug-like chemical space </span></span><em>in silico</em><span>. There have also been simultaneous advancements in structural biology such as cryogenic electron microscopy (cryo-EM) and computational protein-structure prediction, allowing for access to many more high-resolution 3D structures of novel drug-receptor complexes. The convergence of these breakthroughs has positioned structurally-enabled computational methods to be a driving force behind the discovery of novel small molecule therapeutics. This review will give a broad overview of the synergies in recent advances in the fields of computational chemistry, machine learning and structural biology, in particular in the areas of hit identification, hit-to-lead, and lead optimization.</span></p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2021.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39725780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 22
Application of proteomic data in the translation of in vitro observations to associated clinical outcomes 蛋白质组学数据在将体外观察转化为相关临床结果中的应用
Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.06.002
Sibylle Neuhoff , Matthew D. Harwood , Amin Rostami-Hodjegan , Brahim Achour
{"title":"Application of proteomic data in the translation of in vitro observations to associated clinical outcomes","authors":"Sibylle Neuhoff ,&nbsp;Matthew D. Harwood ,&nbsp;Amin Rostami-Hodjegan ,&nbsp;Brahim Achour","doi":"10.1016/j.ddtec.2021.06.002","DOIUrl":"10.1016/j.ddtec.2021.06.002","url":null,"abstract":"<div><p>Translation of information on drug exposure and effect is facilitated by <em>in silico</em> models that enable extrapolation of <em>in vitro</em> measurements to <em>in vivo</em><span> clinical outcomes. These models integrate drug-specific data with information describing physiological processes<span> and pathological changes, including alterations to proteins involved in drug absorption, distribution and elimination. Over the past 15 years, quantitative proteomics<span> has contributed a wealth of protein expression<span> data, which are currently used for a variety of systems pharmacology applications, as a complement or a surrogate for activity of the corresponding proteins. In this review, we explore current and emerging applications of targeted and global (untargeted) proteomics in translational pharmacology as well as strategies for improved integration into model-based drug development.</span></span></span></span></p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2021.06.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39586734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Synthetic carbohydrate-based HIV-1 vaccines 合成碳水化合物为基础的HIV-1疫苗
Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.09.004
Iñaki Bastida , Alberto Fernández-Tejada
{"title":"Synthetic carbohydrate-based HIV-1 vaccines","authors":"Iñaki Bastida ,&nbsp;Alberto Fernández-Tejada","doi":"10.1016/j.ddtec.2020.09.004","DOIUrl":"10.1016/j.ddtec.2020.09.004","url":null,"abstract":"<div><p>An effective prophylactic HIV-1 vaccine is essential in order to contain the HIV/AIDS global pandemic. The discovery of different broadly neutralizing antibodies (bnAbs) in the last decades has enabled the characterization of several minimal epitopes on the HIV envelope (Env) spike, including glycan-dependent fragments. Herein, we provide a brief overview of the progress made on the development of synthetic carbohydrate-based epitope mimics for the elicitation of bnAbs directed to certain regions on Env gp120 protein: the outer domain high-mannose cluster and the variable loops V1V2 and V3. We focus on the design, synthesis and biological evaluation of minimal immunogens and discuss key aspects towards the development of a successful protective vaccine against HIV-1.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2020.09.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39108123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Microcrystal electron diffraction in macromolecular and pharmaceutical structure determination 微晶电子衍射在大分子和药物结构测定中的应用
Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.12.002
Max T.B. Clabbers , Hongyi Xu
{"title":"Microcrystal electron diffraction in macromolecular and pharmaceutical structure determination","authors":"Max T.B. Clabbers ,&nbsp;Hongyi Xu","doi":"10.1016/j.ddtec.2020.12.002","DOIUrl":"10.1016/j.ddtec.2020.12.002","url":null,"abstract":"<div><p>Microcrystal electron diffraction (MicroED) has recently shown to be a promising technique for structure determination in structural biology and pharmaceutical chemistry. Here, we discuss the unique properties of electrons and motivate its use for diffraction experiments. We review the latest developments in MicroED, and illustrate its applications in macromolecular crystallography, fragment screening and structure guided drug discovery. We discuss the perspectives of MicroED in synthetic chemistry and pharmaceutical development. We anticipate that the rapid advances MicroED showcased here will promote further development of electron crystallography and open up new opportunities for drug discovery.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2020.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39592993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Antibody-drug conjugates as targeted therapies: Are we there yet? A critical review of the current clinical landscape 抗体-药物结合作为靶向治疗:我们还在那里吗?对当前临床前景的批判性回顾
Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.07.002
Edit Tarcsa , Magali R. Guffroy , Hadi Falahatpisheh , Colin Phipps , John C. Kalvass
{"title":"Antibody-drug conjugates as targeted therapies: Are we there yet? A critical review of the current clinical landscape","authors":"Edit Tarcsa ,&nbsp;Magali R. Guffroy ,&nbsp;Hadi Falahatpisheh ,&nbsp;Colin Phipps ,&nbsp;John C. Kalvass","doi":"10.1016/j.ddtec.2020.07.002","DOIUrl":"10.1016/j.ddtec.2020.07.002","url":null,"abstract":"<div><p><span><span>Antibody-drug conjugates (ADCs) are targeted therapies with the expectation of broadened therapeutic window due to tumor-specific drug delivery. Recent approvals, including ADCs with a novel payload class, topoisomerase-1 inhibitors, generated renewed excitement in the field. We provide a critical review of approved and late-stage molecules, discuss strategies in </span>solid tumors and ADCs outside oncology. Our pharmacokinetics-based assessment of targeting suggests that ADCs, especially in solid tumors, rely on additional mechanisms for efficacy including slow-release of the payload to the circulation at potentially efficacious levels. Further adjustments in the technology are needed to fulfill the promise of true </span>targeted drug delivery.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2020.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39578705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Bacterial polysaccharides: conformation, dynamics and molecular recognition by antibodies 细菌多糖:构象、动力学和抗体的分子识别
Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.08.002
Marcos Gómez-Redondo , Ana Ardá , Ana Gimeno , Jesús Jiménez-Barbero
{"title":"Bacterial polysaccharides: conformation, dynamics and molecular recognition by antibodies","authors":"Marcos Gómez-Redondo ,&nbsp;Ana Ardá ,&nbsp;Ana Gimeno ,&nbsp;Jesús Jiménez-Barbero","doi":"10.1016/j.ddtec.2020.08.002","DOIUrl":"10.1016/j.ddtec.2020.08.002","url":null,"abstract":"<div><p><span>Bacterial infections are the cause of different severe health conditions and new therapies to combat these pathogens have been widely investigated. Carbohydrates, being complex structures covering the surface of bacteria, are considered relevant targets for antibody and vaccine development. The biological activities in pathogenesis of bacterial capsular </span>polysaccharides and lipopolisaccharides and their unique structures have boosted the study of the minimal antigenic binding epitopes and the structural details of antibody–carbohydrate recognition. This review describes the most recent advances on the field, examining the structure, conformation and dynamics of relevant bacterial carbohydrates and their complexes with antibodies. The understanding of key factors governing the recognition process is fundamental for the progress toward the development of specific and efficient bacterial therapeutics.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2020.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39108118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Erratum regarding missing Declaration of Competing Interest statements in previously published articles 关于先前发表的文章中缺少竞争利益声明的勘误表
Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2021.01.002
{"title":"Erratum regarding missing Declaration of Competing Interest statements in previously published articles","authors":"","doi":"10.1016/j.ddtec.2021.01.002","DOIUrl":"10.1016/j.ddtec.2021.01.002","url":null,"abstract":"","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2021.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39716155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Carbohydrate-based adjuvants 基质佐剂
Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.09.005
Pilar Garcia-Vello , Immacolata Speciale , Fabrizio Chiodo , Antonio Molinaro , Cristina De Castro
{"title":"Carbohydrate-based adjuvants","authors":"Pilar Garcia-Vello ,&nbsp;Immacolata Speciale ,&nbsp;Fabrizio Chiodo ,&nbsp;Antonio Molinaro ,&nbsp;Cristina De Castro","doi":"10.1016/j.ddtec.2020.09.005","DOIUrl":"10.1016/j.ddtec.2020.09.005","url":null,"abstract":"<div><p>Carbohydrate adjuvants are safe and biocompatible compounds usable as sustained delivery systems and stimulants of ongoing humoral and cellular immune responses, being especially suitable for the development of vaccines against intracellular pathogens where alum is useless. The development of new adjuvants is difficult and expensive, however, in the last two years, seven new carbohydrate-based adjuvants have been patented, also there are twelve ongoing clinical trials of vaccines that contain carbohydrate-based adjuvants, as well as numerous publications on their mechanism of action and safety. More research is necessary to improve the existent adjuvants and develop innovative ones.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2020.09.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39108124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
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