Drug Discovery Today: Technologies最新文献_第5页

Synthetic carbohydrate based anti-fungal vaccines 合成碳水化合物抗真菌疫苗

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.11.002

Vadim B. Krylov, Nikolay E. Nifantiev

引用次数: 11

A compact review of molecular property prediction with graph neural networks 用图神经网络预测分子性质的简要综述

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.11.009

Oliver Wieder , Stefan Kohlbacher , Mélaine Kuenemann , Arthur Garon , Pierre Ducrot , Thomas Seidel , Thierry Langer

引用次数: 209

Structure driven compound optimization in targeted protein degradation 靶向蛋白降解中结构驱动的化合物优化

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.11.005

Thomas M. Leissing , Laura M. Luh , Philipp M. Cromm

{"title":"Structure driven compound optimization in targeted protein degradation","authors":"Thomas M. Leissing , Laura M. Luh , Philipp M. Cromm","doi":"10.1016/j.ddtec.2020.11.005","DOIUrl":"10.1016/j.ddtec.2020.11.005","url":null,"abstract":"<div>Small molecule induced protein degradation has created tremendous excitement in drug discovery within recent years. Not being confined to target inhibition and being able to remove disease-causing protein targets via engagement and subsequent ubiquitination has provided scientists with a powerful tool to expand the druggable space. At the center of this approach sits the ternary complex formed between an E3 ubiquitin ligase, the small molecule degrader, and the target protein. A productive ternary complex is pivotal for a ubiquitin to be transferred to a surface lysine of the target protein resulting in poly-ubiquitination which enables recognition and finally degradation by the proteasome. As understanding the ternary complex means understanding the degradation process, many efforts are put into obtaining structural information of the ternary complex and getting a snapshot of the underlying conformations and molecular contacts. Locking this transient trimeric intermediate in a crystalline state has proven to be very demanding but the obtained results have tremendously improved our understanding of small molecule degraders. This review discusses target protein degradation from a structural perspective and highlights the evolution of certain degraders based on the obtained structural insights.</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.2020.11.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39592991","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: 12

The rapidly evolving role of cryo-EM in drug design 低温电子显微镜在药物设计中的快速发展作用

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.12.003

Christoph Wigge, Aleksandar Stefanovic, Mazdak Radjainia

引用次数: 17

Development challenges of high concentration monoclonal antibody formulations 高浓度单克隆抗体制剂的开发挑战

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.08.005

Éva Kollár, Boglárka Balázs, Tímea Tari, István Siró

引用次数: 12

Recent advances in CHO cell line development for recombinant protein production 重组蛋白生产CHO细胞系的研究进展

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2021.02.003

Borbála Tihanyi, László Nyitray

{"title":"Recent advances in CHO cell line development for recombinant protein production","authors":"Borbála Tihanyi, László Nyitray","doi":"10.1016/j.ddtec.2021.02.003","DOIUrl":"10.1016/j.ddtec.2021.02.003","url":null,"abstract":"<div>Recombinant proteins used in biomedical research, diagnostics and different therapies are mostly produced in Chinese hamster ovary cells in the pharmaceutical industry. These biotherapeutics, monoclonal antibodies in particular, have shown remarkable market growth in the past few decades. The increasing demand for high amounts of biologics requires continuous optimization and improvement of production technologies. Research aims at discovering better means and methods for reaching higher volumetric capacity, while maintaining stable product quality. An increasing number of complex novel protein therapeutics, such as viral antigens, vaccines, bi- and tri-specific monoclonal antibodies, are currently entering industrial production pipelines. These biomolecules are, in many cases, difficult to express and require tailored product-specific solutions to improve their transient or stable production. All these requirements boost the development of more efficient expression optimization systems and high-throughput screening platforms to facilitate the design of product-specific cell line engineering and production strategies. In this minireview, we provide an overview on recent advances in CHO cell line development, targeted genome manipulation techniques, selection systems and screening methods currently used in recombinant protein production.</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.2021.02.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39716157","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: 67

Role of carbohydrate antigens in antifungal glycoconjugate vaccines and immunotherapy 糖类抗原在抗真菌糖结合疫苗和免疫治疗中的作用

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2021.02.002

Linda Del Bino, Maria Rosaria Romano

{"title":"Role of carbohydrate antigens in antifungal glycoconjugate vaccines and immunotherapy","authors":"Linda Del Bino, Maria Rosaria Romano","doi":"10.1016/j.ddtec.2021.02.002","DOIUrl":"10.1016/j.ddtec.2021.02.002","url":null,"abstract":"<div>The emergence of fungal infection is a growing public health concern that in the latest years is becoming a serious threat to humans, particularly for immunocompromised individuals. Invasive fungal infections (IFIs), which are associated with significant morbidity and mortality, are on the rise due to the availability of only a few old antifungal agents. In addition to this, the growing use of antibiotics makes the population increasingly susceptible to these infections. Since carbohydrates are the main component of the fungal cell wall, the study of fungal glycans as potential targets for the fight against IFIs has aroused much interest in recent decades. In most fungal species the saccharides of the core are made up of chitin and β-glucans, while the outer layer carbohydrates vary according to the fungal species, such as mannans for Candida albicans, galactomannans for Aspergillus fumigatus hyphae, α-glucans for Aspergillus fumigatus and Cryptococcus neoformans, glucuronoxylomannans (GXM) and galactoxylomannans (GalXM) for Criptococcus neoformans. Being surface antigens, fungal carbohydrates are a logical target for the development of antifungal glycoconjugate vaccines and for immunotherapy with monoclonal antibodies. This review summarizes recent findings on active and passive immunization strategies based on fungal carbohydrates explored preclinically for three of the major fungal pathogens: Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus.</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.2021.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39717123","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

Career development in fragment-based drug discovery 基于片段的药物发现的职业发展

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.10.001

A.K.S. Romasanta , P.C. van der Sijde , M.J. Smit , I.J.P. de Esch , W. Jahnke , J.E. van Muijlwijk-Koezen

{"title":"Career development in fragment-based drug discovery","authors":"A.K.S. Romasanta , P.C. van der Sijde , M.J. Smit , I.J.P. de Esch , W. Jahnke , J.E. van Muijlwijk-Koezen","doi":"10.1016/j.ddtec.2020.10.001","DOIUrl":"10.1016/j.ddtec.2020.10.001","url":null,"abstract":"<div>The pharmaceutical industry is highly reliant on researchers who not only possess the technical knowledge but also the professional skills to collaborate in drug development. To prepare future practitioners to thrive in this interdisciplinary environment, Innovative Training Networks (ITNs) have become increasingly important in doctoral training. In this piece, we explore the benefits of these ITNs in training future practitioners in drug discovery. Through a bibliometric review, we find that the top researchers in fragment-based drug discovery have a high degree of collaboration and mobility across institutes. We then investigate which aspects of the ITN training program enable PhD students to gain these skills. We find that secondments, the short-term stays that students have in partner research institutes, are useful in preparing students to have both broad knowledge of drug discovery and specialization in their field of interest. Aside from imparting technical skills, we find that the collaborative environment in ITNs enables students to communicate better and to work effectively in teams. Doctoral students benefit by being exposed to relevant experiences that they can later apply as they navigate through the complex web of relationships and competencies in the industry. We conclude by recommending best practices to further improve ITNs in the training of future practitioners.</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.2020.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39578702","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: 2

Organometallic compounds in drug discovery: Past, present and future 药物发现中的有机金属化合物:过去、现在和未来

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2019.06.001

Yih Ching Ong, Gilles Gasser

引用次数: 24

In vitro functional characterization of biosimilar therapeutic antibodies 生物类似药治疗性抗体的体外功能表征

Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI: 10.1016/j.ddtec.2020.11.010

Júlia Anna Láng, Zsófia Cselovszkiné Balogh, Mónika Fizilné Nyitrai, Cintia Juhász, Anna Katalin Baráné Gilicze, Attila Iliás, Zsolt Zólyomi, Csaba Bodor, Erzsébet Rábai

{"title":"In vitro functional characterization of biosimilar therapeutic antibodies","authors":"Júlia Anna Láng, Zsófia Cselovszkiné Balogh, Mónika Fizilné Nyitrai, Cintia Juhász, Anna Katalin Baráné Gilicze, Attila Iliás, Zsolt Zólyomi, Csaba Bodor, Erzsébet Rábai","doi":"10.1016/j.ddtec.2020.11.010","DOIUrl":"10.1016/j.ddtec.2020.11.010","url":null,"abstract":"<div>The key factor in successful development and marketing of biosimilar antibodies is a deep understanding of their critical quality attributes and the ability to control them. Comprehensive functional characterization is therefore at the heart of the process and is a crucial part of regulatory requirements. Establishment of a scientifically sound molecule-specific functional in vitro assay panel requires diligent planning and high flexibility in order to respond to both regulatory requirements and the ever-changing demands relevant to the different stages of the development and production process. Relevance of the chosen assays to the in vivo mechanism of action is of key importance to the stepwise evidence-based demonstration of biosimilarity. Use of a sound interdisciplinary approach and orthogonal state-of-the-art techniques is also unavoidable for gaining in-depth understanding of the biosimilar candidate.The aim of the present review is to give a snapshot on the methodic landscape as depicted by the available literature discussing the in vitro techniques used for the functional characterization of approved biosimilar therapeutic antibodies. Emerging hot topics of the field and relevant structure-function relationships are also highlighted.</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.2020.11.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39578708","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: 6