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Machine learning-based brightfield detection of anti-fibrotic effects in a 3D retinal fibrosis model. 基于机器学习的明场检测在三维视网膜纤维化模型中的抗纤维化作用。
IF 2.7
SLAS discovery : advancing life sciences R & D Pub Date : 2026-10-11 DOI: 10.1016/j.slasd.2026.100343
Thomas Hofstetter, Özlem Yavas Grining, Christophe Roubeix, Peter D Westenskow, David A Fluri
{"title":"Machine learning-based brightfield detection of anti-fibrotic effects in a 3D retinal fibrosis model.","authors":"Thomas Hofstetter, Özlem Yavas Grining, Christophe Roubeix, Peter D Westenskow, David A Fluri","doi":"10.1016/j.slasd.2026.100343","DOIUrl":"10.1016/j.slasd.2026.100343","url":null,"abstract":"<p><p>Three-dimensional (3D) spheroid and microtissue models are increasingly used in phenotypic drug discovery, yet their scalability for high-throughput screening often remains limited, constrained by the cost and complexity of conventional imaging-based readouts. Here, we present a morphology-based screening approach using low-resolution brightfield images of human retinal pigment epithelium microtissues (hRPE-MTs) to identify fibrotic and non-fibrotic phenotypes. The results of this study demonstrate that extracting geometric, intensity, and texture features from segmented spheroids enables quantitative characterization of fibrosis-associated morphological changes. Machine learning classifiers trained on these features effectively discriminated between fibrotic and non-fibrotic hRPE-MTs. Collectively, these findings indicate that label-free brightfield morphology encodes sufficient information to support scalable phenotypic screening in 3D fibrosis models. This approach provides a low-complexity and broadly accessible strategy for early-stage drug discovery.</p>","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100343"},"PeriodicalIF":2.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171457","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
Temperature-related intensity change (TRIC)-based high-throughput screening enables the discovery of small molecule CD28 binders. 基于温度相关强度变化（TRIC）的高通量筛选使CD28小分子结合物得以发现。
IF 2.7
SLAS discovery : advancing life sciences R & D Pub Date : 2025-09-01 Epub Date: 2025-08-05 DOI: 10.1016/j.slasd.2025.100256
Laura Calvo-Barreiro, Saurabh Upadhyay, Moustafa T Gabr
{"title":"Temperature-related intensity change (TRIC)-based high-throughput screening enables the discovery of small molecule CD28 binders.","authors":"Laura Calvo-Barreiro, Saurabh Upadhyay, Moustafa T Gabr","doi":"10.1016/j.slasd.2025.100256","DOIUrl":"10.1016/j.slasd.2025.100256","url":null,"abstract":"<p><p>CD28 is a pivotal costimulatory receptor involved in T cell activation and immune regulation, positioning it as a key therapeutic target for inflammatory diseases, including inflammatory bowel disease (IBD). Despite its potential, small molecules targeting CD28 are still limited. To fill this gap, we developed a high-throughput screening (HTS) platform based on Temperature-Related Intensity Change (TRIC) technology, enabling rapid, immobilization-free screening of chemical libraries of small molecules. Using the Dianthus instrument, we applied our optimized TRIC assay for CD28 (signal-to-noise ratio of 21.99) to screen two MedChemExpress libraries: Small Molecule Immuno-Oncology Compounds (SMIOC) and Protein-Protein Interaction Inhibitors (PPII), identifying 50 initial hits. Following exclusion of compounds with dye interference or aggregation artifacts, 12 candidates were prioritized for further validation. Microscale thermophoresis (MST) confirmed dose-dependent binding of seven compounds to CD28, with affinities in the micromolar range. Surface plasmon resonance (SPR) further validated two compounds, EABP 02,303 and CTEP, as CD28 binders. These results demonstrate that our TRIC-based HTS platform is robust, scalable, and effective for identifying small molecule CD28 binders. The incorporation of orthogonal validation supports the reliability of our findings and highlights the feasibility of small-molecule discovery targeting CD28.</p>","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100256"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801187","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
A high-throughput response to the SARS-CoV-2 pandemic. 高通量应对 SARS-CoV-2 大流行。
SLAS discovery : advancing life sciences R & D Pub Date : 2024-07-01 Epub Date: 2024-05-16 DOI: 10.1016/j.slasd.2024.100160
Lynn Rasmussen, Shalisa Sanders, Melinda Sosa, Sara McKellip, N Miranda Nebane, Yohanka Martinez-Gzegozewska, Andrew Reece, Pedro Ruiz, Anna Manuvakhova, Ling Zhai, Brooke Warren, Aliyah Curry, Qinghua Zeng, J Robert Bostwick, Paige N Vinson
{"title":"A high-throughput response to the SARS-CoV-2 pandemic.","authors":"Lynn Rasmussen, Shalisa Sanders, Melinda Sosa, Sara McKellip, N Miranda Nebane, Yohanka Martinez-Gzegozewska, Andrew Reece, Pedro Ruiz, Anna Manuvakhova, Ling Zhai, Brooke Warren, Aliyah Curry, Qinghua Zeng, J Robert Bostwick, Paige N Vinson","doi":"10.1016/j.slasd.2024.100160","DOIUrl":"10.1016/j.slasd.2024.100160","url":null,"abstract":"<p><p>Four years after the beginning of the COVID-19 pandemic, it is important to reflect on the events that have occurred during that time and the knowledge that has been gained. The response to the pandemic was rapid and highly resourced; it was also built upon a foundation of decades of federally funded basic and applied research. Laboratories in government, pharmaceutical, academic, and non-profit institutions all played roles in advancing pre-2020 discoveries to produce clinical treatments. This perspective provides a summary of how the development of high-throughput screening methods in a biosafety level 3 (BSL-3) environment at Southern Research Institute (SR) contributed to pandemic response efforts. The challenges encountered are described, including those of a technical nature as well as those of working under the pressures of an unpredictable virus and pandemic.</p>","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100160"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961194","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
Optimising cell-based bioassays via integrated design of experiments (ixDoE) - A practical guide. 通过综合实验设计(ixDoE)优化基于细胞的生物测定-实用指南。
SLAS discovery : advancing life sciences R & D Pub Date : 2022-10-01 DOI: 10.2139/ssrn.4107411
J. Solzin, K. Eppler, B. Knapp, H. Buchner, E. Bluhmki
{"title":"Optimising cell-based bioassays via integrated design of experiments (ixDoE) - A practical guide.","authors":"J. Solzin, K. Eppler, B. Knapp, H. Buchner, E. Bluhmki","doi":"10.2139/ssrn.4107411","DOIUrl":"https://doi.org/10.2139/ssrn.4107411","url":null,"abstract":"For process optimisation Design of Experiments (DoE) has long been established as a more powerful strategy than a One Factor at a Time approach. Nevertheless, DoE is not widely used especially in the field of cell-based bioassay development although it is known that complex interactions often exist. We believe that biopharmaceutical manufacturers are reluctant to move beyond standard practices due to the perceived costs, efforts, and complexity. We therefore introduce the integrated DoE (ixDoE) approach to target a smarter use of DoEs in the bioassay setting, specifically in optimising resources and time. Where in a standard practice 3 to 4 separate DoEs would be performed, our ixDoE approach includes the necessary statistical inference from only a single experimental set. Hence, we advocate for an innovative, ixDoE approach accompanied by a suitable statistical analysis strategy and present this as a practical guide for a typical bioassay development from basic research to biopharmaceutical industry.","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85648679","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: 2
Kaposi's sarcoma-associated herpes virus-derived microRNA K12-1 over-activates the PI3K/Akt pathway to facilitate cancer progression in HIV-related gastrointestinal Kaposi's sarcoma. 卡波西氏肉瘤相关疱疹病毒衍生的microRNA K12-1过度激活PI3K/Akt通路，促进hiv相关胃肠道卡波西氏肉瘤的癌症进展。
SLAS discovery : advancing life sciences R & D Pub Date : 2022-04-01 DOI: 10.1016/j.slasd.2022.04.001
X. Huang, W. Rao, Chun Wang, Jiajie Lu, Ziqiong Li, Wenjie Kong, Yan Feng, T. Xu, Rziya Rziya, F. Gao
{"title":"Kaposi's sarcoma-associated herpes virus-derived microRNA K12-1 over-activates the PI3K/Akt pathway to facilitate cancer progression in HIV-related gastrointestinal Kaposi's sarcoma.","authors":"X. Huang, W. Rao, Chun Wang, Jiajie Lu, Ziqiong Li, Wenjie Kong, Yan Feng, T. Xu, Rziya Rziya, F. Gao","doi":"10.1016/j.slasd.2022.04.001","DOIUrl":"https://doi.org/10.1016/j.slasd.2022.04.001","url":null,"abstract":"","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87956671","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: 2
Development of a High-Throughput Assay to Identify Inhibitors of the Ubiquitin-Conjugating Enzyme UBCH10. 一种高通量测定方法鉴定泛素偶联酶UBCH10抑制剂。
SLAS discovery : advancing life sciences R & D Pub Date : 2022-03-01 DOI: 10.1016/j.slasd.2022.03.007
P. Cléroux, L. Voisin, S. Meloche
{"title":"Development of a High-Throughput Assay to Identify Inhibitors of the Ubiquitin-Conjugating Enzyme UBCH10.","authors":"P. Cléroux, L. Voisin, S. Meloche","doi":"10.1016/j.slasd.2022.03.007","DOIUrl":"https://doi.org/10.1016/j.slasd.2022.03.007","url":null,"abstract":"","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79049590","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: 2
Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay. 基于细胞的Lumit p-ERK免疫分析分析致癌KRAS突变药物。
SLAS discovery : advancing life sciences R & D Pub Date : 2022-03-01 DOI: 10.1016/j.slasd.2022.03.001
Matthew R Swiatnicki, Laurie Engel, Riva Shrestha, Juliano Alves, S. Goueli, H. Zegzouti
{"title":"Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay.","authors":"Matthew R Swiatnicki, Laurie Engel, Riva Shrestha, Juliano Alves, S. Goueli, H. Zegzouti","doi":"10.1016/j.slasd.2022.03.001","DOIUrl":"https://doi.org/10.1016/j.slasd.2022.03.001","url":null,"abstract":"","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85785046","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: 1
Three-Dimensional Cell Cultures in Drug Discovery and Development. 药物发现与开发中的三维细胞培养。
SLAS discovery : advancing life sciences R & D Pub Date : 2017-01-01 DOI: 10.1177/2472555217696795
Ye Fang, R. Eglen
{"title":"Three-Dimensional Cell Cultures in Drug Discovery and Development.","authors":"Ye Fang, R. Eglen","doi":"10.1177/2472555217696795","DOIUrl":"https://doi.org/10.1177/2472555217696795","url":null,"abstract":"The past decades have witnessed significant efforts toward the development of three-dimensional (3D) cell cultures as systems that better mimic in vivo physiology. Today, 3D cell cultures are emerging, not only as a new tool in early drug discovery but also as potential therapeutics to treat disease. In this review, we assess leading 3D cell culture technologies and their impact on drug discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting. We also discuss the implementation of these technologies in compound identification, screening, and development, ranging from disease modeling to assessment of efficacy and safety profiles.","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":"1984 1","pages":"2472555217696795"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82228766","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: 266
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