Pub Date : 2025-04-01Epub Date: 2025-02-28DOI: 10.1016/j.slasd.2025.100224
Aislinn Mayfield , Xin Zhang, Ivan Efremov, Michael G Kauffman, John F Reilly, Bahareh Eftekharzadeh
Biomolecular condensates (BMCs) are crucial for cellular organization and function, and their dysregulation is linked to neurological, oncologic and inflammatory diseases. This highlights the need for advanced investigative tools leading to targeted BMC therapeutics. To address this need, Nereid Therapeutics uses Corelet™ technology and an automated high-throughput screening (HTS) platform to precisely quantify phase separation events and identify BMC modulators for previously undruggable targets. Hundreds of thousands of small molecules have been screened utilizing Corelet technology, yielding small molecule BMC-modulating compounds which serve as the basis for the development of targeted therapies for diseases with high unmet need.
{"title":"Corelet™ platform: Precision high throughput screening for targeted drug discovery of biomolecular condensates","authors":"Aislinn Mayfield , Xin Zhang, Ivan Efremov, Michael G Kauffman, John F Reilly, Bahareh Eftekharzadeh","doi":"10.1016/j.slasd.2025.100224","DOIUrl":"10.1016/j.slasd.2025.100224","url":null,"abstract":"<div><div>Biomolecular condensates (BMCs) are crucial for cellular organization and function, and their dysregulation is linked to neurological, oncologic and inflammatory diseases. This highlights the need for advanced investigative tools leading to targeted BMC therapeutics. To address this need, Nereid Therapeutics uses Corelet™ technology and an automated high-throughput screening (HTS) platform to precisely quantify phase separation events and identify BMC modulators for previously undruggable targets. Hundreds of thousands of small molecules have been screened utilizing Corelet technology, yielding small molecule BMC-modulating compounds which serve as the basis for the development of targeted therapies for diseases with high unmet need.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100224"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538195","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}
Pub Date : 2025-04-01Epub Date: 2025-03-14DOI: 10.1016/j.slasd.2025.100226
Elisabeth Bäck , Jessica Bjärkby , Leire Escudero-Ibarz , Stefan Tångefjord , Johan Jirholt , Mei Ding
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive age-related lung disease with an average survival of 3–5 years post-diagnosis if left untreated. It is characterized by lung fibrosis, inflammation, and destruction of lung architecture, leading to worsening respiratory symptoms and physiological impairment, ultimately culminating in progressive respiratory failure. The development of novel therapeutics for the treatment of IPF represents a significant unmet medical need. Fibroblast to myofibroblast transition (FMT) in response to fibrogenic mediators such as transforming growth factor beta 1 (TGF-β1) has been identified as a key cellular phenotype driving the formation of myofibroblasts and lung fibrosis in IPF. Establishing a robust and high-throughput in vitro human FMT assay is crucial for uncovering new disease targets and for efficiently screening compounds for the advancement of novel therapeutics aimed at targeting myofibroblast activity. However, creating a robust FMT assay suitable for high-throughput drug screening has proven challenging due to the requisite level of automation.
In this study, we focus on evaluating different automation approaches for liquid exchange and compound dosing in the human FMT assay. A semi-automated assay, capable of screening a large number of compounds that inhibit TGF-β1-induced FMT in both Normal Human Lung Fibroblasts (NHLF) and IPF-patient derived Disease Human Lung Fibroblasts (IPF-DHLF), has been successfully developed and optimized. We demonstrate that the optimized FMT assay using liquid handling automation exhibits great assay reproducibility, shows good assay translation using human lung fibroblasts from normal healthy versus IPF-patients, and demonstrates acceptable human primary donor variability. This allows for the standardization of comparisons of compound anti-fibrotic potency across IPF projects.
{"title":"Enhancing throughput and robustness of the fibroblast to myofibroblast transition assay","authors":"Elisabeth Bäck , Jessica Bjärkby , Leire Escudero-Ibarz , Stefan Tångefjord , Johan Jirholt , Mei Ding","doi":"10.1016/j.slasd.2025.100226","DOIUrl":"10.1016/j.slasd.2025.100226","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive age-related lung disease with an average survival of 3–5 years post-diagnosis if left untreated. It is characterized by lung fibrosis, inflammation, and destruction of lung architecture, leading to worsening respiratory symptoms and physiological impairment, ultimately culminating in progressive respiratory failure. The development of novel therapeutics for the treatment of IPF represents a significant unmet medical need. Fibroblast to myofibroblast transition (FMT) in response to fibrogenic mediators such as transforming growth factor beta 1 (TGF-β1) has been identified as a key cellular phenotype driving the formation of myofibroblasts and lung fibrosis in IPF. Establishing a robust and high-throughput in vitro human FMT assay is crucial for uncovering new disease targets and for efficiently screening compounds for the advancement of novel therapeutics aimed at targeting myofibroblast activity. However, creating a robust FMT assay suitable for high-throughput drug screening has proven challenging due to the requisite level of automation.</div><div>In this study, we focus on evaluating different automation approaches for liquid exchange and compound dosing in the human FMT assay. A semi-automated assay, capable of screening a large number of compounds that inhibit TGF-β1-induced FMT in both Normal Human Lung Fibroblasts (NHLF) and IPF-patient derived Disease Human Lung Fibroblasts (IPF-DHLF), has been successfully developed and optimized. We demonstrate that the optimized FMT assay using liquid handling automation exhibits great assay reproducibility, shows good assay translation using human lung fibroblasts from normal healthy versus IPF-patients, and demonstrates acceptable human primary donor variability. This allows for the standardization of comparisons of compound anti-fibrotic potency across IPF projects.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100226"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639935","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}
Pub Date : 2025-04-01Epub Date: 2025-04-08DOI: 10.1016/j.slasd.2025.100231
Timothy P. Spicer, Louis D. Scampavia
{"title":"SLAS special issue editorial 2025: Outcomes from antiviral drug discovery for pathogens of pandemic concern","authors":"Timothy P. Spicer, Louis D. Scampavia","doi":"10.1016/j.slasd.2025.100231","DOIUrl":"10.1016/j.slasd.2025.100231","url":null,"abstract":"","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100231"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-15DOI: 10.1016/j.slasd.2025.100209
Lauren Toms, Lorna FitzPatrick, Philip Auckland
At the turn of the century a fundamental resolution barrier in fluorescence microscopy known as the diffraction limit was broken, giving rise to the field of super-resolution microscopy. Subsequent nanoscopic investigation with visible light revolutionised our understanding of how previously unknown molecular features give rise to the emergent behaviour of cells. It transpires that the devil is in these fine molecular details, and essential nanoscale processes were found everywhere researchers chose to look. Now, after nearly two decades, super-resolution microscopy has begun to address previously unmet challenges in the study of human disease and is poised to become a pivotal tool in drug discovery.
{"title":"Super-resolution microscopy as a drug discovery tool","authors":"Lauren Toms, Lorna FitzPatrick, Philip Auckland","doi":"10.1016/j.slasd.2025.100209","DOIUrl":"10.1016/j.slasd.2025.100209","url":null,"abstract":"<div><div>At the turn of the century a fundamental resolution barrier in fluorescence microscopy known as the diffraction limit was broken, giving rise to the field of super-resolution microscopy. Subsequent nanoscopic investigation with visible light revolutionised our understanding of how previously unknown molecular features give rise to the emergent behaviour of cells. It transpires that the devil is in these fine molecular details, and essential nanoscale processes were found everywhere researchers chose to look. Now, after nearly two decades, super-resolution microscopy has begun to address previously unmet challenges in the study of human disease and is poised to become a pivotal tool in drug discovery.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100209"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017977","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}
Pub Date : 2025-03-01Epub Date: 2025-01-11DOI: 10.1016/j.slasd.2025.100210
Francisca Arez , Lena Preiss , Isabella Ramella Gal , Sofia P. Rebelo , Lassina Badolo , Catarina Brito , Thomas Spangenberg , Paula M. Alves
Primary human hepatocytes (PHHs) are the preferred cell source to address liver function. Despite originating from the native tissue, one of the bottlenecks when using primary material is the donor-to-donor variability. Cryopreserved PHHs offer a high number of cells from the same donor and standardization of cell isolation and cryopreservation procedures, mitigating some of the inter-donor variability. Still, PHHs from different commercial sources present variability in vitro in several parameters, including viability post-thawing, plating capacity, aggregation potential and culture longevity. Here we combine stirred-tank culture systems, which allow robust aggregation processes, and co-culture approaches with the HepaRG cell line to generate spheroids from cryopreserved PHHs. By employing small-scale stirred-tank culture systems we could cope with the scarce availability and high cost of primary material. In the optimized co-culture conditions we could generate PHH:HepaRG spheroids from 12 donors acquired from 4 different commercial sources. All PHHs showed similar aggregation profiles, forming small compact heterotypic spheroids as early as 3 days in co-culture and were maintained for at least 5 weeks in culture. The heterotypic spheroids maintained the hepatocyte polarization and identity and showed metabolization capacity for 5 main phase I metabolizing enzymes, namely CYP3A4, CYP2C9, CYP1A2, CYP2D6, and CYP2C8. Moreover, the heterotypic spheroids showed the capacity to metabolize a novel compound under clinical development, showing their potential to be employed in drug discovery applications.
Overall, we present a robust aggregation strategy for cryopreserved PHHs from different suppliers, applicable for pharmacological and toxicological in vitro research.
{"title":"Heterotypic spheroids as a strategy for 3D culture of cryopreserved primary human hepatocytes in stirred-tank systems","authors":"Francisca Arez , Lena Preiss , Isabella Ramella Gal , Sofia P. Rebelo , Lassina Badolo , Catarina Brito , Thomas Spangenberg , Paula M. Alves","doi":"10.1016/j.slasd.2025.100210","DOIUrl":"10.1016/j.slasd.2025.100210","url":null,"abstract":"<div><div>Primary human hepatocytes (PHHs) are the preferred cell source to address liver function. Despite originating from the native tissue, one of the bottlenecks when using primary material is the donor-to-donor variability. Cryopreserved PHHs offer a high number of cells from the same donor and standardization of cell isolation and cryopreservation procedures, mitigating some of the inter-donor variability. Still, PHHs from different commercial sources present variability <em>in vitro</em> in several parameters, including viability post-thawing, plating capacity, aggregation potential and culture longevity. Here we combine stirred-tank culture systems, which allow robust aggregation processes, and co-culture approaches with the HepaRG cell line to generate spheroids from cryopreserved PHHs. By employing small-scale stirred-tank culture systems we could cope with the scarce availability and high cost of primary material. In the optimized co-culture conditions we could generate PHH:HepaRG spheroids from 12 donors acquired from 4 different commercial sources. All PHHs showed similar aggregation profiles, forming small compact heterotypic spheroids as early as 3 days in co-culture and were maintained for at least 5 weeks in culture. The heterotypic spheroids maintained the hepatocyte polarization and identity and showed metabolization capacity for 5 main phase I metabolizing enzymes, namely CYP3A4, CYP2C9, CYP1A2, CYP2D6, and CYP2C8. Moreover, the heterotypic spheroids showed the capacity to metabolize a novel compound under clinical development, showing their potential to be employed in drug discovery applications.</div><div>Overall, we present a robust aggregation strategy for cryopreserved PHHs from different suppliers, applicable for pharmacological and toxicological in vitro research.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100210"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980832","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}
Pub Date : 2025-03-01Epub Date: 2025-01-06DOI: 10.1016/j.slasd.2025.100208
Marcus Y. Chin , David A. Joy , Madhuja Samaddar, Anil Rana, Johann Chow, Takashi Miyamoto, Meredith Calvert
Mitochondria undergo dynamic morphological changes depending on cellular cues, stress, genetic factors, or disease. The structural complexity and disease-relevance of mitochondria have stimulated efforts to generate image analysis tools for describing mitochondrial morphology for therapeutic development. Using high-content analysis, we measured multiple morphological parameters and employed unbiased feature clustering to identify the most robust pair of texture metrics that described mitochondrial state. Here, we introduce a novel image analysis pipeline to enable rapid and accurate profiling of mitochondrial morphology in various cell types and pharmacological perturbations. We applied a high-content adapted implementation of our tool, MitoProfilerHC, to quantify mitochondrial morphology changes in i) a mammalian cell dose response study and ii) compartment-specific drug effects in primary neurons. Next, we expanded the usability of our pipeline by using napari, a Python-powered image analysis tool, to build an open-source version of MitoProfiler and validated its performance and applicability. In conclusion, we introduce MitoProfiler as both a high-content-based and an open-source method to accurately quantify mitochondrial morphology in cells, which we anticipate to greatly facilitate mechanistic discoveries in mitochondrial biology and disease.
{"title":"Novel high-content and open-source image analysis tools for profiling mitochondrial morphology in neurological cell models","authors":"Marcus Y. Chin , David A. Joy , Madhuja Samaddar, Anil Rana, Johann Chow, Takashi Miyamoto, Meredith Calvert","doi":"10.1016/j.slasd.2025.100208","DOIUrl":"10.1016/j.slasd.2025.100208","url":null,"abstract":"<div><div>Mitochondria undergo dynamic morphological changes depending on cellular cues, stress, genetic factors, or disease. The structural complexity and disease-relevance of mitochondria have stimulated efforts to generate image analysis tools for describing mitochondrial morphology for therapeutic development. Using high-content analysis, we measured multiple morphological parameters and employed unbiased feature clustering to identify the most robust pair of texture metrics that described mitochondrial state. Here, we introduce a novel image analysis pipeline to enable rapid and accurate profiling of mitochondrial morphology in various cell types and pharmacological perturbations. We applied a high-content adapted implementation of our tool, MitoProfilerHC, to quantify mitochondrial morphology changes in i) a mammalian cell dose response study and ii) compartment-specific drug effects in primary neurons. Next, we expanded the usability of our pipeline by using napari, a Python-powered image analysis tool, to build an open-source version of MitoProfiler and validated its performance and applicability. In conclusion, we introduce MitoProfiler as both a high-content-based and an open-source method to accurately quantify mitochondrial morphology in cells, which we anticipate to greatly facilitate mechanistic discoveries in mitochondrial biology and disease.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100208"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960156","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}
Pub Date : 2025-03-01Epub Date: 2025-01-17DOI: 10.1016/j.slasd.2025.100215
Kasper P. Lundquist , Isabella Romeo , Raffaele B. Puglielli , Maëlle Pestalozzi , Marie L. Gram , Emily S. Hudson , Ofri Levi , Yoav S. Arava , Charlotte H. Gotfredsen , Mads H. Clausen
Fragment-based screening is an efficient method for early-stage drug discovery. In this study, we aimed to create a fragment library optimized for producing high hit rates against RNA targets. RNA has historically been an underexplored target, but recent research suggests potential for optimizing small molecule libraries for RNA binding. We extended this concept to fragment libraries to produce an RNA optimized fluorinated fragment library. We then screened this library, alongside two non-RNA optimized fragment libraries, against three RNA targets: the human cytoplasmic A-site and the S. cerevisiae tRNAAsp anticodon stem loop with and without nucleobase modifications. The screens yielded 24, 31, and 20 hits against the respective targets. Importantly, statistical analysis confirmed a significant overrepresentation of hits in our RNA optimized library. Based on these findings, we propose guidelines for developing RNA optimized fragment libraries. We hope the guidelines will help expediting fragment-based ligand discovery for RNA targets and contribute to presenting RNA as a promising target in drug discovery.
{"title":"Design, synthesis, and screening of an RNA optimized fluorinated fragment library","authors":"Kasper P. Lundquist , Isabella Romeo , Raffaele B. Puglielli , Maëlle Pestalozzi , Marie L. Gram , Emily S. Hudson , Ofri Levi , Yoav S. Arava , Charlotte H. Gotfredsen , Mads H. Clausen","doi":"10.1016/j.slasd.2025.100215","DOIUrl":"10.1016/j.slasd.2025.100215","url":null,"abstract":"<div><div>Fragment-based screening is an efficient method for early-stage drug discovery. In this study, we aimed to create a fragment library optimized for producing high hit rates against RNA targets. RNA has historically been an underexplored target, but recent research suggests potential for optimizing small molecule libraries for RNA binding. We extended this concept to fragment libraries to produce an RNA optimized fluorinated fragment library. We then screened this library, alongside two non-RNA optimized fragment libraries, against three RNA targets: the human cytoplasmic A-site and the <em>S. cerevisiae</em> tRNA<sup>Asp</sup> anticodon stem loop with and without nucleobase modifications. The screens yielded 24, 31, and 20 hits against the respective targets. Importantly, statistical analysis confirmed a significant overrepresentation of hits in our RNA optimized library. Based on these findings, we propose guidelines for developing RNA optimized fragment libraries. We hope the guidelines will help expediting fragment-based ligand discovery for RNA targets and contribute to presenting RNA as a promising target in drug discovery.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100215"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017964","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}
Pub Date : 2025-03-01Epub Date: 2025-01-15DOI: 10.1016/j.slasd.2025.100212
Nandini Sharma , Yuka Otsuka , Louis Scampavia , Timothy P. Spicer , Jarrod B. French
Metabolic reprogramming of purine biosynthesis is a hallmark of cancer metabolism and represents a critical vulnerability. The enzyme phosphoribosylformylglycinamidine synthase (PFAS) catalyzes the fourth step in de novo purine biosynthesis and has been demonstrated to be prognostic for survival of liver cancer. Despite the importance of this protein as a drug target, there are no known specific inhibitors of PFAS activity. Here, we describe a new continuous, spectrophotometric assay for the synthase domain of PFAS that is amenable to high-throughput screening (HTS). This mechanism-based fluorescent assay makes use of the acid phosphatase substrate, 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP). PFAS catalyzes the turnover of DiFMUP with a KM of 108 ± 7 µM. After optimization and miniaturization of the assay for 1,536-well format, we conducted a pilot HTS using the LOPAC1280 library. The assay performed extremely well, with an average Z′ of 0.94 ± 0.02, average signal to noise of 5.01 ± 0.06, excellent inter plate correlation, and a hit rate of 1.18 %. This assay provides a critically needed tool to advance the study of PFAS enzymology and will be foundational for the discovery of small molecule inhibitors both as functional probes and for the basis of new drug development.
{"title":"A high throughput assay for phosphoribosylformylglycinamidine synthase","authors":"Nandini Sharma , Yuka Otsuka , Louis Scampavia , Timothy P. Spicer , Jarrod B. French","doi":"10.1016/j.slasd.2025.100212","DOIUrl":"10.1016/j.slasd.2025.100212","url":null,"abstract":"<div><div>Metabolic reprogramming of purine biosynthesis is a hallmark of cancer metabolism and represents a critical vulnerability. The enzyme phosphoribosylformylglycinamidine synthase (PFAS) catalyzes the fourth step in <em>de novo</em> purine biosynthesis and has been demonstrated to be prognostic for survival of liver cancer. Despite the importance of this protein as a drug target, there are no known specific inhibitors of PFAS activity. Here, we describe a new continuous, spectrophotometric assay for the synthase domain of PFAS that is amenable to high-throughput screening (HTS). This mechanism-based fluorescent assay makes use of the acid phosphatase substrate, 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP). PFAS catalyzes the turnover of DiFMUP with a <em>K<sub>M</sub></em> of 108 ± 7 µM. After optimization and miniaturization of the assay for 1,536-well format, we conducted a pilot HTS using the LOPAC<sup>1280</sup> library. The assay performed extremely well, with an average Z′ of 0.94 ± 0.02, average signal to noise of 5.01 ± 0.06, excellent inter plate correlation, and a hit rate of 1.18 %. This assay provides a critically needed tool to advance the study of PFAS enzymology and will be foundational for the discovery of small molecule inhibitors both as functional probes and for the basis of new drug development.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100212"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017937","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}
Pub Date : 2025-03-01Epub Date: 2025-01-16DOI: 10.1016/j.slasd.2025.100214
Martin P. Schwalm , Stefan Knapp
Cancer research, cancer treatment, and the field of chemical biology are examples which heavily rely on the discovery of selective kinase inhibitors. While determining on-target potency is often feasible for most laboratories, the equally critical but frequently neglected selectivity screening remains less accessible to the broader scientific community. This limitation can stem from various factors, such as the unavailability of a large number of purified kinases or the costs associated with commercial screening systems. To address these challenges and enable a wider range of scientists, this protocol leverages a commercial kinome selectivity screen to facilitate a low-cost, two-day, single-plate selectivity screen against 192 kinases.
{"title":"Single-plate kinome screening in live-cells to enable highly cost-efficient kinase inhibitor profiling","authors":"Martin P. Schwalm , Stefan Knapp","doi":"10.1016/j.slasd.2025.100214","DOIUrl":"10.1016/j.slasd.2025.100214","url":null,"abstract":"<div><div>Cancer research, cancer treatment, and the field of chemical biology are examples which heavily rely on the discovery of selective kinase inhibitors. While determining on-target potency is often feasible for most laboratories, the equally critical but frequently neglected selectivity screening remains less accessible to the broader scientific community. This limitation can stem from various factors, such as the unavailability of a large number of purified kinases or the costs associated with commercial screening systems. To address these challenges and enable a wider range of scientists, this protocol leverages a commercial kinome selectivity screen to facilitate a low-cost, two-day, single-plate selectivity screen against 192 kinases.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"31 ","pages":"Article 100214"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017975","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}
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