SLAS Discovery最新文献

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Characterisation of high throughput screening outputs for small molecule degrader discovery 用于发现小分子降解剂的高通量筛选结果的特征描述
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-05-24 DOI: 10.1016/j.slasd.2024.100162
Lillie E. Bell , Catherine Bardelle , Martin J Packer , Johanna Kastl , Geoffrey A. Holdgate , Gareth Davies
{"title":"Characterisation of high throughput screening outputs for small molecule degrader discovery","authors":"Lillie E. Bell ,&nbsp;Catherine Bardelle ,&nbsp;Martin J Packer ,&nbsp;Johanna Kastl ,&nbsp;Geoffrey A. Holdgate ,&nbsp;Gareth Davies","doi":"10.1016/j.slasd.2024.100162","DOIUrl":"10.1016/j.slasd.2024.100162","url":null,"abstract":"<div><p>Targeted protein degradation is an important mechanism carried out by the cellular machinery, one that is gaining momentum as an exploitable strategy for the development of drug-like compounds. Molecules which are able to induce proximity between elusive therapeutic targets of interest and E3 ligases which subsequently leads to proteasomal degradation of the target are beginning to decrease the percentage of the human proteome described as undruggable. Therefore, having the ability to screen for, and understand the mechanism of, such molecules is becoming an increasingly attractive scientific focus. We have established a number of cascade experiments including cell-based assays and orthogonal triage steps to provide annotation to the selectivity and mechanism of action for compounds identified as putative degraders from a primary high throughput screen against a high value oncology target. We will describe our current position, using PROTACs as proof-of-concept, on the analysis of these novel outputs and highlight challenges encountered.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 5","pages":"Article 100162"},"PeriodicalIF":3.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000248/pdfft?md5=dc288a87ff98b6fd26cc25724269aadb&pid=1-s2.0-S2472555224000248-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Creating a more strategic small molecule biophysical hit characterization workflow 创建更具战略性的小分子生物物理命中表征工作流程。
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-05-07 DOI: 10.1016/j.slasd.2024.100159
Christopher Fotsch , Debaleena Basu , Ryan Case , Qing Chen , Pratibha C. Koneru , Mei-Chu Lo , Rachel Ngo , Pooja Sharma , Amit Vaish , Xiang Yi , Stephan G. Zech , Peter Hodder
{"title":"Creating a more strategic small molecule biophysical hit characterization workflow","authors":"Christopher Fotsch ,&nbsp;Debaleena Basu ,&nbsp;Ryan Case ,&nbsp;Qing Chen ,&nbsp;Pratibha C. Koneru ,&nbsp;Mei-Chu Lo ,&nbsp;Rachel Ngo ,&nbsp;Pooja Sharma ,&nbsp;Amit Vaish ,&nbsp;Xiang Yi ,&nbsp;Stephan G. Zech ,&nbsp;Peter Hodder","doi":"10.1016/j.slasd.2024.100159","DOIUrl":"10.1016/j.slasd.2024.100159","url":null,"abstract":"<div><p>To confirm target engagement of hits from our high-throughput screening efforts, we ran biophysical assays on several hundreds of hits from 15 different high-throughput screening campaigns. Analyzing the biophysical assay results from these screening campaigns led us to conclude that we could be more strategic in our biophysical analysis of hits by first confirming activity in a thermal shift assay (TSA) and then confirming activity in either a surface plasmon resonance (SPR) assay or a temperature-related intensity change (TRIC) assay. To understand how this new workflow shapes the quality of the final hits, we compared TSA/SPR or TSA/TRIC confirmed and unconfirmed hits to one another using four measures of compound quality: quantitative estimate of drug-likeness (QED), Pan-Assay Interference Compounds (PAINS), promiscuity, and aqueous solubility. In general, we found that the biophysically confirmed hits performed better in the compound quality metrics than the unconfirmed hits, demonstrating that our workflow not only confirmed target engagement of the hits but also enriched for higher quality hits.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 4","pages":"Article 100159"},"PeriodicalIF":3.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000212/pdfft?md5=389ec9b1863fb13b54ef5a3823355f2d&pid=1-s2.0-S2472555224000212-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing scaffold-free spheroid models: 3D cell bioprinting method for metastatic HSC3–Oral squamous carcinoma cell line 增强无支架球体模型:转移性 HSC3-口腔鳞癌细胞系的三维细胞生物打印方法
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-05-01 DOI: 10.1016/j.slasd.2024.100158
Taís Bacelar Sacramento de Araújo , Raphael Luís Rocha Nogueira , Leonardo de Oliveira Siquara da Rocha , Iasmin Nogueira Bastos , Rosane Borges Dias , Bruno Solano De Freitas Souza , Daniel William Lambert , Ricardo D. Coletta , Viviane Aline Oliveira Silva , Clarissa A. Gurgel Rocha
{"title":"Enhancing scaffold-free spheroid models: 3D cell bioprinting method for metastatic HSC3–Oral squamous carcinoma cell line","authors":"Taís Bacelar Sacramento de Araújo ,&nbsp;Raphael Luís Rocha Nogueira ,&nbsp;Leonardo de Oliveira Siquara da Rocha ,&nbsp;Iasmin Nogueira Bastos ,&nbsp;Rosane Borges Dias ,&nbsp;Bruno Solano De Freitas Souza ,&nbsp;Daniel William Lambert ,&nbsp;Ricardo D. Coletta ,&nbsp;Viviane Aline Oliveira Silva ,&nbsp;Clarissa A. Gurgel Rocha","doi":"10.1016/j.slasd.2024.100158","DOIUrl":"https://doi.org/10.1016/j.slasd.2024.100158","url":null,"abstract":"<div><p>3D <em>in vitro</em> systems offer advantages over the shortcomings of two-dimensional models by simulating the morphological and functional features of <em>in vivo</em>-like environments, such as cell-cell and cell-extracellular matrix interactions, as well as the co-culture of different cell types. Nevertheless, these systems present technical challenges that limit their potential in cancer research requiring cell line- and culture-dependent standardization. This protocol details the use of a magnetic 3D bioprinting method and other associated techniques (cytotoxicity assay and histological analysis) using oral squamous cell carcinoma cell line, HSC3, which offer advantages compared to existing widely used approaches. This protocol is particularly timely, as it validates magnetic bioprinting as a method for the rapid deployment of 3D cultures as a tool for compound screening and development of heterotypic cultures such as co-culture of oral squamous cell carcinoma cells with cancer-associated fibroblasts (HSC3/CAFs).</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 4","pages":"Article 100158"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000200/pdfft?md5=65af641e1cc59f0ba7520fa27146fec1&pid=1-s2.0-S2472555224000200-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
POLARISED views and FRETting about probe modulation assays: Learning from High Throughput Screening 关于探针调制测定的 POLARISED 视图和 FRETting:从高通量筛选中学习
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-04-18 DOI: 10.1016/j.slasd.2024.100156
Alice Lanne , Catherine Bardelle , Gareth Davies , Antonia Turberville , Hannah Semple , Rachel Moore , Geoffrey A. Holdgate
{"title":"POLARISED views and FRETting about probe modulation assays: Learning from High Throughput Screening","authors":"Alice Lanne ,&nbsp;Catherine Bardelle ,&nbsp;Gareth Davies ,&nbsp;Antonia Turberville ,&nbsp;Hannah Semple ,&nbsp;Rachel Moore ,&nbsp;Geoffrey A. Holdgate","doi":"10.1016/j.slasd.2024.100156","DOIUrl":"https://doi.org/10.1016/j.slasd.2024.100156","url":null,"abstract":"<div><p>Fluorescent probe modulation assays are a widely used approach to monitor displacement or stabilisation of fluorescently labelled tool ligands by test compounds. These assays allow an optical read-out of probe-receptor binding and can be used to detect compounds that compete with the labelled ligand, either directly or indirectly. Probes for both orthosteric and allosteric sites are often employed. The method can also be used to identify test compounds that may stabilise the ternary complex, offering an opportunity to discover novel molecular glues. The utility of these fluorescence-based assays within high-throughput screening has been facilitated by the use of streptavidin labelled terbium as a donor and access to a range of different acceptor fluorophores. During 2023, the High-throughput Screening group at AstraZeneca carried out 8 high-throughput screens using these approaches. In this manuscript we will present the types of assays used, an overview of the timelines for assay development and screening, the application of orthogonal artefact methods to aid hit finding and the results of the screens in terms of hit rate and the number of compounds identified with IC<sub>50</sub> values of better than 30 µM. Learning across the development, execution and analysis of these screens will be presented.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 4","pages":"Article 100156"},"PeriodicalIF":3.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000182/pdfft?md5=31508b5b2d14cbf4e0c02d5d7e69cecf&pid=1-s2.0-S2472555224000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aldehyde Dehydrogenase 2 (ALDH2): A novel sorafenib target in hepatocellular carcinoma unraveled by the proteome-wide cellular thermal shift assay 醛脱氢酶 2 (ALDH2):通过全蛋白质组细胞热转移测定揭示的肝癌索拉非尼新靶点
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-04-01 DOI: 10.1016/j.slasd.2024.100154
Inês C. Ferreira , Estefania Torrejón , Bernardo Abecasis , Bruno M. Alexandre , Ricardo A. Gomes , Chris Verslype , Jos van Pelt , Ana Barbas , Daniel Simão , Tiago M. Bandeiras , Alessio Bortoluzzi , Sofia P. Rebelo
{"title":"Aldehyde Dehydrogenase 2 (ALDH2): A novel sorafenib target in hepatocellular carcinoma unraveled by the proteome-wide cellular thermal shift assay","authors":"Inês C. Ferreira ,&nbsp;Estefania Torrejón ,&nbsp;Bernardo Abecasis ,&nbsp;Bruno M. Alexandre ,&nbsp;Ricardo A. Gomes ,&nbsp;Chris Verslype ,&nbsp;Jos van Pelt ,&nbsp;Ana Barbas ,&nbsp;Daniel Simão ,&nbsp;Tiago M. Bandeiras ,&nbsp;Alessio Bortoluzzi ,&nbsp;Sofia P. Rebelo","doi":"10.1016/j.slasd.2024.100154","DOIUrl":"10.1016/j.slasd.2024.100154","url":null,"abstract":"<div><p>Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete. To build upon the current understanding, we used the Cellular Thermal Shift Assay (CETSA) coupled to Mass Spectrometry (CETSA-MS) to monitor compound binding to its target proteins in the cellular context on a proteome-wide scale. Among the potential sorafenib targets, we identified aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a major role in alcohol metabolism. We validated the interaction of sorafenib with ALDH2 by orthogonal methods using pure recombinant protein, proving that this interaction is not mediated by other cellular components. Moreover, we showed that sorafenib inhibits ALDH2 activity, supporting a functional role for this interaction. Finally, we were able to demonstrate that both ALDH2 protein expression and activity were reduced in sorafenib-resistant cells compared to the parental cell line. Overall, our study allowed the identification of ALDH2 as a novel sorafenib target and sheds light on its potential role in both hepatocellular carcinoma and sorafenib resistance condition.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 3","pages":"Article 100154"},"PeriodicalIF":3.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000169/pdfft?md5=e39307bdcc31a11896db9724bd824787&pid=1-s2.0-S2472555224000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Establishment, optimization and validation of a fluorescence polarization-based high-throughput screening assay targeting cathepsin L inhibitors 建立、优化和验证基于荧光偏振的 Cathepsin L 抑制剂高通量筛选试验。
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-03-20 DOI: 10.1016/j.slasd.2024.100153
Wenwen Zhou , Baoqing You , Xiaomeng Zhao , Shuyi Si , Yan Li , Jing Zhang
{"title":"Establishment, optimization and validation of a fluorescence polarization-based high-throughput screening assay targeting cathepsin L inhibitors","authors":"Wenwen Zhou ,&nbsp;Baoqing You ,&nbsp;Xiaomeng Zhao ,&nbsp;Shuyi Si ,&nbsp;Yan Li ,&nbsp;Jing Zhang","doi":"10.1016/j.slasd.2024.100153","DOIUrl":"10.1016/j.slasd.2024.100153","url":null,"abstract":"<div><p>Cathepsin L (CTSL), a lysosomal cysteine proteinase, is primarily dedicated to the metabolic turnover of intracellular proteins. It is involved in various physiological processes and contributes to pathological conditions such as viral infection, tumor invasion and metastasis, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, and other ailments. The coronavirus disease 2019 (COVID-19), with its rapid global spread and significant mortality, has been a worldwide epidemic since the late 2019s. Notably, CTSL plays a role in the processing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, providing a potential avenue to block coronavirus host cell entry and thereby inhibit SARS-CoV-2 infection in humans. In this study, we have developed a novel method using fluorescence polarization (FP) for screening CTSL inhibitors in a high-throughput format. The optimized assay demonstrated its appropriateness for high-throughput screening (HTS) with a Z-factor of 0.9 in a 96-well format. Additionally, the IC<sub>50</sub> of the known inhibitor, Z-Phe-Tyr-CHO, was determined to be 188.50 ± 46.88 nM. Upon screening over 2000 small molecules, we identified, for the first time, the anti-CTSL properties of a benzothiazoles derivative named IMB 8015. This work presents a novel high-throughput approach and its application in discovering and evaluating CTSL inhibitors.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 3","pages":"Article 100153"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000157/pdfft?md5=531dea274a50b4826ec3758fe007d67d&pid=1-s2.0-S2472555224000157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Outline and background for the EU-OS solubility prediction challenge 欧盟海洋观测系统溶解度预测挑战赛的概要和背景。
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-03-20 DOI: 10.1016/j.slasd.2024.100155
Wenyu Wang , Jing Tang , Andrea Zaliani
{"title":"Outline and background for the EU-OS solubility prediction challenge","authors":"Wenyu Wang ,&nbsp;Jing Tang ,&nbsp;Andrea Zaliani","doi":"10.1016/j.slasd.2024.100155","DOIUrl":"10.1016/j.slasd.2024.100155","url":null,"abstract":"<div><p>In June 2022, EU-OS came to the decision to make public a solubility data set of 100+K compounds obtained from several of the EU-OS proprietary screening compound collections. Leveraging on the interest of SLAS for screening scientific development it was decided to launch a joint EUOS-SLAS competition within the chemoinformatics and machine learning (ML) communities. The competition was open to real world computation experts, for the best, most predictive, classification model of compound solubility. The aim of the competition was multiple: from a practical side, the winning model should then serve as a cornerstone for future solubility predictions having used the largest training set so far publicly available. From a higher project perspective, the intent was to focus the energies and experiences, even if professionally not precisely coming from Pharma R&amp;D; to address the issue of how to predict compound solubility. Here we report how the competition was ideated and the practical aspects of conducting it within the Kaggle framework, leveraging of the versatility and the open-source nature of this data science platform. Consideration on results and challenges encountered have been also examined.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 4","pages":"Article 100155"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000170/pdfft?md5=31adf40156a4682f7a09408654d5d462&pid=1-s2.0-S2472555224000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-throughput nephelometry methodology for qualitative determination of aqueous solubility of chemical libraries 用于定性测定化学文库水溶性的高通量尼泊金测定法
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-03-06 DOI: 10.1016/j.slasd.2024.100149
Jose Brea , Maria J. Varela , Geert A. Daudey , Maria I. Loza
{"title":"High-throughput nephelometry methodology for qualitative determination of aqueous solubility of chemical libraries","authors":"Jose Brea ,&nbsp;Maria J. Varela ,&nbsp;Geert A. Daudey ,&nbsp;Maria I. Loza","doi":"10.1016/j.slasd.2024.100149","DOIUrl":"10.1016/j.slasd.2024.100149","url":null,"abstract":"<div><p>The purpose of the protocol reported in this work is the solubility profiling of large chemical libraries using nephelometry. This technique allows the qualitative classification of compounds as highly, moderately, or poorly water-soluble. The described methodology is not intended to yield quantitative solubility values of the studied compounds but can be used as a primary solubility assessment of large chemical libraries, to guide hit prioritization after High Throughput Screening (HTS) campaigns.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 3","pages":"Article 100149"},"PeriodicalIF":3.1,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S247255522400011X/pdfft?md5=a9b754a03190a54dd2fb6bb4cd348956&pid=1-s2.0-S247255522400011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protocol for kinetic mode potassium channel assays on common plate readers and microscopes 在普通平板阅读器和显微镜上进行动力学模式钾通道检测的规程
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-03-02 DOI: 10.1016/j.slasd.2024.100148
Emery Smith , Louise Dickson , Philip Pickford , Anna Rowland , Justin Shumate , Katherine Perez , Louis Scampavia , Derek Hernandez , Timothy P. Spicer
{"title":"Protocol for kinetic mode potassium channel assays on common plate readers and microscopes","authors":"Emery Smith ,&nbsp;Louise Dickson ,&nbsp;Philip Pickford ,&nbsp;Anna Rowland ,&nbsp;Justin Shumate ,&nbsp;Katherine Perez ,&nbsp;Louis Scampavia ,&nbsp;Derek Hernandez ,&nbsp;Timothy P. Spicer","doi":"10.1016/j.slasd.2024.100148","DOIUrl":"https://doi.org/10.1016/j.slasd.2024.100148","url":null,"abstract":"<div><p>Fluorescence-based potassium channel assays are typically run on expensive, hard to obtain, fluorescence imaging kinetic plate readers that are uncommon in most laboratories. Here we describe the use of the Brilliant Thallium Snapshot assay to conduct an endpoint potassium channel assay, so that it can be used across multiple plate reader platforms that are more common in many labs. These methods will allow users to identify modulators of potassium channels. For this work, we have taken a kinetic mode Molecular Devices FLIPR based protocol and adapted it to be utilized on endpoint plate readers, such as the BMG Labtech PHERAstar, to identify activators of GIRK channels in CHO cells. We demonstrate that both plate readers are functionally competent at generating excellent Z’ values which makes them ideally suited to finding corollary hits from the Sigma LOPAC 1,280 screening collection. Importantly, this assay has also been validated using a high content reader, demonstrating the possibility of spatially resolving signals from individual cells within a mixed cell population. The compendium of these results shows the flexibility, accessibility and functionality of endpoint-compatible potassium channel assay readouts on more common plate readers.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"29 3","pages":"Article 100148"},"PeriodicalIF":3.1,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2472555224000108/pdfft?md5=fb5fd387899cb3c039a7cbf52f959893&pid=1-s2.0-S2472555224000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Establishment of a high-content imaging assay for tau aggregation in hiPSC-derived neurons differentiated from two protocols to routinely evaluate compounds and genetic perturbations 建立一种高浓度成像检测方法,用于检测由两种方案分化而来的 hiPSC 神经元中 tau 的聚集情况,以便对化合物和遗传扰动进行常规评估。
IF 3.1 4区 生物学
SLAS Discovery Pub Date : 2024-03-01 DOI: 10.1016/j.slasd.2023.12.009
Lamiaa Bahnassawy , Nathalie Nicolaisen , Christopher Untucht , Benjamin Mielich-Süss , Lydia Reinhardt , Janina S. Ried , Martina P. Morawe , Daniela Geist , Anja Finck , Elke Käfer , Jürgen Korffmann , Matthew Townsend , Brinda Ravikumar , Viktor Lakics , Miroslav Cik , Peter Reinhardt
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