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A High Throughput Assay to Identify Modulators of Death Receptor 3 (DR3). 一种鉴定死亡受体3 （DR3）调节剂的高通量试验。
IF 2.7
SLAS discovery : advancing life sciences R & D Pub Date : 2026-05-05 DOI: 10.1016/j.slasd.2026.100312
Emery Smith, Joshua K Parker, Izan Gonzalez Fayos, Nicholas R Stan, Louis Scampavia, Thomas Kodadek, Timothy P Spicer
{"title":"A High Throughput Assay to Identify Modulators of Death Receptor 3 (DR3).","authors":"Emery Smith, Joshua K Parker, Izan Gonzalez Fayos, Nicholas R Stan, Louis Scampavia, Thomas Kodadek, Timothy P Spicer","doi":"10.1016/j.slasd.2026.100312","DOIUrl":"https://doi.org/10.1016/j.slasd.2026.100312","url":null,"abstract":"<p><p>Association of the TNF-like cytokine 1A (TL1A) with Death Receptor 3 (DR3) triggers a signaling cascade in T cells that results in the increased AP-1- and NF-κB-mediated expression of inflammation-promoting gene products. Dysregulation of TL1A/DR3 signaling is a major contributor to many autoimmune diseases, cancers, and other conditions yet there is a dearth of small molecule regulators of this pathway. Here we report a cell-based high throughput screen of 8,000 compounds of compounds that yielded 12 antagonists but no agonists of this pathway.</p>","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100312"},"PeriodicalIF":2.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847267","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
Cleaving through complexity: Pan-serotype fluorimetric assays for the dengue virus proteases. 通过复杂性切割：登革病毒蛋白酶的泛血清型荧光测定。
IF 2.7
SLAS discovery : advancing life sciences R & D Pub Date : 2026-04-28 DOI: 10.1016/j.slasd.2026.100310
Miguel M Macedo, Johannes Lang, Katharina Eckstein, Selina L Muffler, Leah M Glanzmann, Christian Klein, Mila-M Leuthold
{"title":"Cleaving through complexity: Pan-serotype fluorimetric assays for the dengue virus proteases.","authors":"Miguel M Macedo, Johannes Lang, Katharina Eckstein, Selina L Muffler, Leah M Glanzmann, Christian Klein, Mila-M Leuthold","doi":"10.1016/j.slasd.2026.100310","DOIUrl":"https://doi.org/10.1016/j.slasd.2026.100310","url":null,"abstract":"<p><p>Dengue virus (DENV) is a health threat with global impact. The viral NS2B/NS3 protease is responsible for viral polyprotein processing at a number of cleavage sites. This cleavage is indispensable for establishing productive infection, highlighting the pivotal role of the DENV protease. As such this enzyme is a promising target for the development of antivirals. The absence of a standardized enzymatic assay procedure, using diverse assay conditions and protease constructs, poses a challenge in evaluation of inhibition data. Here, we describe the analysis and comparison of assay parameters for proteases of all four circulating DENV1 to DENV4 serotypes, eventually enabling high-throughput screening (HTS). DENV1-4 proteases were used in the detailed exploration of biochemical assay conditions and a number of FRET substrates as well as AMC-coupled fluorogenic substrates were characterized. The DENV1 protease showed the lowest levels of substrate cleavage, with k<sub>cat</sub> values several folds below the others (0.03 s<sup>-1</sup> vs. 0.4 s<sup>-1</sup>). This prompted us to design novel substrates based on the 2A/2B and 2B/3 cleavage sites. Enzyme kinetics and inhibition of the DENV1-4 proteases were characterized under two widely applicable assay conditions. The feasibility to use these conditions for HTS was verified in 384-well format. Based on the results, we present two robust assay protocols, suitable to examine activity and inhibition of proteases of all four DENV serotypes in parallel, allowing for HTS. A well-characterized assay procedure can enhance coherence in DENV protease studies, contributing to progress in antiviral research.</p>","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100310"},"PeriodicalIF":2.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824435","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
Beyond fluorescence: A critical look at AI-powered brightfield analysis for T-cell killing assays. 超越荧光：对人工智能驱动的t细胞杀伤分析的批判性观察。
IF 2.7
SLAS discovery : advancing life sciences R & D Pub Date : 2026-03-20 DOI: 10.1016/j.slasd.2026.100307
Xiaoman Liu, Zihan Gao, Jiachun Xu
{"title":"Beyond fluorescence: A critical look at AI-powered brightfield analysis for T-cell killing assays.","authors":"Xiaoman Liu, Zihan Gao, Jiachun Xu","doi":"10.1016/j.slasd.2026.100307","DOIUrl":"10.1016/j.slasd.2026.100307","url":null,"abstract":"<p><p>This comment evaluates dela Cruz-Chuh et al.'s AI-based label-free workflow for analyzing T-cell mediated tumor killing via brightfield imaging. The study's core strengths include eliminating fluorescent labeling artifacts, achieving comparable consistency to conventional segmentation-based methods, and accommodating phenotypically diverse cancer cells without manual parameter tuning-addressing key bottlenecks in immunotherapy screening. However, critical considerations persist: the binary \"killing/non-killing\" classification framework may insufficiently resolve low-level or partial cytotoxicity, as evidenced by six false negatives; generalizability to non-adherent hematological malignancies or alternative effector cells remains untested; and the model lacks interpretability regarding morphological features driving cytotoxicity predictions. Additionally, performance across variable imaging platforms or culture conditions is unevaluated, limiting translational reproducibility. Despite these gaps, the workflow advances high-throughput immunotherapy screening efficiency. Future studies incorporating multi-class training, validation across diverse cancer types, and mechanistic decoding of AI-predicted features will strengthen its rigor and broader applicability in drug discovery.</p>","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100307"},"PeriodicalIF":2.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500946","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
Response to letter regarding "AI‑based analysis of label‑free live‑cell imaging of T‑cell-mediated tumor killing". 关于“基于AI的T细胞介导肿瘤杀伤无标记活细胞成像分析”的回复。
IF 2.7
SLAS discovery : advancing life sciences R & D Pub Date : 2026-03-20 DOI: 10.1016/j.slasd.2026.100306
Josefa Dela Cruz-Chuh, Daniel Siegismund, John Moffat, Stephan Heyse, Katherine R Kozak, Stephan Steigele
{"title":"Response to letter regarding \"AI‑based analysis of label‑free live‑cell imaging of T‑cell-mediated tumor killing\".","authors":"Josefa Dela Cruz-Chuh, Daniel Siegismund, John Moffat, Stephan Heyse, Katherine R Kozak, Stephan Steigele","doi":"10.1016/j.slasd.2026.100306","DOIUrl":"10.1016/j.slasd.2026.100306","url":null,"abstract":"","PeriodicalId":74806,"journal":{"name":"SLAS discovery : advancing life sciences R & D","volume":" ","pages":"100306"},"PeriodicalIF":2.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500940","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
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