SLAS DiscoveryPub Date : 2023-07-01DOI: 10.1016/j.slasd.2023.02.003
Andrew Lim
{"title":"Mathematical relationships between control group variability and assay quality metrics","authors":"Andrew Lim","doi":"10.1016/j.slasd.2023.02.003","DOIUrl":"10.1016/j.slasd.2023.02.003","url":null,"abstract":"<div><p>Assay quality metrics have been used in various high-throughput screening (HTS) campaigns to indicate assay quality. Z’-factor has become one of the most widely used metrics, along with other metrics such as standardised mean difference (SSMD). In using these metrics, it is important to understand how these metrics can be impacted by the separation between control groups (indicated by the HZ ratio) and the coefficient of variation (CV) within each control group. In this paper, several mathematical equations have been derived to understand the relationship between assay quality metrics (such as Z’-factor and SSMD) and control group datasets (summarised by CV and HZ). These equations increase our understanding of the factors that improve assay quality metrics, thus providing a quantitative means to visualise how affecting control groups can impact assay quality metrics.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 5","pages":"Pages 203-210"},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10146422","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}
SLAS DiscoveryPub Date : 2023-07-01DOI: 10.1016/j.slasd.2023.04.001
Martin Winter , Roman P. Simon , Tim T. Häbe, Robert Ries, Yuting Wang, David Kvaskoff, Amaury Fernández-Montalván, Andreas H. Luippold, Frank H. Büttner, Wolfgang Reindl
{"title":"Label-free high-throughput screening via acoustic ejection mass spectrometry put into practice","authors":"Martin Winter , Roman P. Simon , Tim T. Häbe, Robert Ries, Yuting Wang, David Kvaskoff, Amaury Fernández-Montalván, Andreas H. Luippold, Frank H. Büttner, Wolfgang Reindl","doi":"10.1016/j.slasd.2023.04.001","DOIUrl":"10.1016/j.slasd.2023.04.001","url":null,"abstract":"<div><p>Acoustic droplet ejection-open port interface-mass spectrometry (ADE-OPI-MS) is a novel label-free analytical technique, promising to become a versatile readout for high-throughput screening (HTS) applications. The recent introduction of ADE-OPI-MS devices to the laboratory equipment market, paired with their compatibility with laboratory automation platforms, should facilitate the adoption of this technology by a broader community. Towards this goal, instrument robustness in the context of HTS campaigns - where up to millions of samples in complex matrices are tested in a short time frame - represents a major challenge, which explains the absence of detailed literature reports on this subject. Here, we present the results of our first fully automated HTS campaign, based on the ADE-OPI-MS technology, aiming to identify inhibitors of a metabolic enzyme in a >1 million compound library. The report encompasses the assay development and validation steps, as well as the adaptation for HTS requirements, where refinement of the capillary cleaning concept was crucial for final success. Altogether, our study unequivocally demonstrates the applicability of the ADE-OPI-MS technology for HTS-based drug discovery.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 5","pages":"Pages 240-246"},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846151","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}
SLAS DiscoveryPub Date : 2023-07-01DOI: 10.1016/j.slasd.2023.03.004
Nicolas Julian Scheuplein , Theresa Lohr , Mirella Vivoli Vega , Dyan Ankrett , Florian Seufert , Lukas Kirchner , Nicholas J. Harmer , Ulrike Holzgrabe
{"title":"Fluorescent probe for the identification of potent inhibitors of the macrophage infectivity potentiator (Mip) protein of Burkholderia pseudomallei","authors":"Nicolas Julian Scheuplein , Theresa Lohr , Mirella Vivoli Vega , Dyan Ankrett , Florian Seufert , Lukas Kirchner , Nicholas J. Harmer , Ulrike Holzgrabe","doi":"10.1016/j.slasd.2023.03.004","DOIUrl":"10.1016/j.slasd.2023.03.004","url":null,"abstract":"<div><p>The macrophage infectivity potentiator (Mip) protein belongs to the immunophilin superfamily. This class of enzymes catalyzes the interconversion between the <em>cis</em> and <em>trans</em> configuration of proline-containing peptide bonds. Mip has been shown to be important for the virulence of a wide range of pathogenic microorganisms, including the Gram-negative bacterium <em>Burkholderia pseudomallei</em>. Small molecules derived from the natural product rapamycin, lacking its immunosuppression-inducing moiety, inhibit Mip's peptidyl-prolyl <em>cis</em>-<em>trans</em> isomerase (PPIase) activity and lead to a reduction in pathogen load <em>in vitro</em>. Here, a fluorescence polarization assay (FPA) to enable the screening and effective development of BpMip inhibitors was established. A fluorescent probe was prepared, derived from previous pipecolic scaffold Mip inhibitors labeled with fluorescein. This probe showed moderate affinity for BpMip and enabled a highly robust FPA suitable for screening large compound libraries with medium- to high-throughput (Z factor ∼ 0.89) to identify potent new inhibitors. The FPA results are consistent with data from the protease-coupled PPIase assay. Analysis of the temperature dependence of the probe's binding highlighted that BpMip's ligand binding is driven by enthalpic rather than entropic effects. This has considerable consequences for the use of low-temperature kinetic assays.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 5","pages":"Pages 211-222"},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9845386","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}
SLAS DiscoveryPub Date : 2023-07-01DOI: 10.1016/j.slasd.2023.03.005
Henry Kim , Nathalie Weidner , Céline Ronin , Emmanuel Klein , James A. Roper , Barbro Kahl-Knutson , Kristoffer Peterson , Hakon Leffler , Ulf J. Nilsson , Anders Pedersen , Fredrik R. Zetterberg , Robert J. Slack
{"title":"Evaluating the affinity and kinetics of small molecule glycomimetics for human and mouse galectin-3 using surface plasmon resonance","authors":"Henry Kim , Nathalie Weidner , Céline Ronin , Emmanuel Klein , James A. Roper , Barbro Kahl-Knutson , Kristoffer Peterson , Hakon Leffler , Ulf J. Nilsson , Anders Pedersen , Fredrik R. Zetterberg , Robert J. Slack","doi":"10.1016/j.slasd.2023.03.005","DOIUrl":"10.1016/j.slasd.2023.03.005","url":null,"abstract":"<div><p>Galectin-3 is a beta-galactoside-binding mammalian lectin that is one of a 15-member galectin family that can bind several cell surface glycoproteins via its carbohydrate recognition domain (CRD). As a result, it can influence a range of cellular processes including cell activation, adhesion and apoptosis. Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine <em>K<sub>D</sub></em> values. Surface plasmon resonance (SPR) has not been widely used for compound screening and in this study it was used to compare human and mouse galectin-3 affinity measures between FP and SPR, as well as investigate compound kinetics. The <em>K<sub>D</sub></em> estimates for a set of compounds selected from mono- and di-saccharides with affinities across a 550-fold range, correlated well between FP and SPR assay formats for both human and mouse galectin-3. Increases in affinity for compounds binding to human galectin-3 were driven by changes in both <em>k<sub>on</sub></em> and <em>k<sub>off</sub></em> whilst for mouse galectin-3 this was primarily due to <em>k<sub>on</sub></em>. The reduction in affinity observed between human to mouse galectin-3 was also comparable between assay formats. SPR has been shown to be a viable alternative to FP for early drug discovery screening and determining <em>K<sub>D</sub></em> values. In addition, it can also provide early kinetic characterisation of small molecule galectin-3 glycomimetics with robust <em>k<sub>on</sub></em> and <em>k<sub>off</sub></em> values generated in a high throughput manner.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 5","pages":"Pages 233-239"},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9789149","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}
SLAS DiscoveryPub Date : 2023-06-01DOI: 10.1016/j.slasd.2023.03.003
Ramya Visvanathan , Tadanobu Utsuki , Daniel E. Beck , Emma Lendy , Kuai-lin Sun , Yinghui Liu , Kirk W. Hering , Andrew Mesecar , Zhong-Yin Zhang , Karson S. Putt
{"title":"A novel fluorogenic reporter substrate for 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2): Application to high-throughput screening for activators to treat Alzheimer's disease","authors":"Ramya Visvanathan , Tadanobu Utsuki , Daniel E. Beck , Emma Lendy , Kuai-lin Sun , Yinghui Liu , Kirk W. Hering , Andrew Mesecar , Zhong-Yin Zhang , Karson S. Putt","doi":"10.1016/j.slasd.2023.03.003","DOIUrl":"10.1016/j.slasd.2023.03.003","url":null,"abstract":"<div><p>A rare coding variant in PLCγ2 (P522R) expressed in microglia induces a mild activation of enzymatic activity when compared to wild-type. This mutation is reported to be protective against the cognitive decline associated with late-onset Alzheimer's disease (LOAD) and therefore, activation of wild-type PLCγ2 has been suggested as a potential therapeutic target for the prevention and treatment of LOAD. Additionally, PLCγ2 has been associated with other diseases such as cancer and some autoimmune disorders where mutations with much greater increases in PLCγ2 activity have been identified. Here, pharmacological inhibition may provide a therapeutic effect. In order to facilitate our investigation of the activity of PLCγ2, we developed an optimized fluorogenic substrate to monitor enzymatic activity in aqueous solution. This was accomplished by first exploring the spectral properties of various “turn-on” fluorophores. The most promising turn-on fluorophore was incorporated into a water-soluble PLCγ2 reporter substrate, which we named C8CF3-coumarin. The ability of PLCγ2 to enzymatically process C8CF3-coumarin was confirmed, and the kinetics of the reaction were determined. Reaction conditions were optimized to identify small molecule activators, and a pilot screen of the Library of Pharmacologically Active Compounds 1280 (LOPAC<sub>1280</sub>) was performed with the goal of identifying small molecule activators of PLCγ2. The optimized screening conditions allowed identification of potential PLCγ2 activators and inhibitors, thus demonstrating the feasibility of this approach for high-throughput screening.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 4","pages":"Pages 170-179"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/5f/nihms-1905403.PMC10251139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596188","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}
SLAS DiscoveryPub Date : 2023-06-01DOI: 10.1016/j.slasd.2023.04.003
Somaya A. Abdel-Rahman , Longfei Zhang , Moustafa T. Gabr
{"title":"Development of a high-throughput TR-FRET screening assay for LAG-3/FGL1 interaction","authors":"Somaya A. Abdel-Rahman , Longfei Zhang , Moustafa T. Gabr","doi":"10.1016/j.slasd.2023.04.003","DOIUrl":"10.1016/j.slasd.2023.04.003","url":null,"abstract":"<div><p>Lymphocyte activation gene 3 (LAG-3) is a negative immune checkpoint and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. Fibrinogen-like protein 1 (FGL1) is a major LAG-3 functional ligand that is upregulated in various human cancers. LAG-3 positive T cells bind FGL1 expressed by cancer cells, which inhibits T-cell activation and cytokine secretion <em>via</em> indirect blocking of T cell receptor (TCR) signaling. High expression of LAG-3 and FGL1 in patients with solid tumors is associated with drug resistance and decreased survival in response to FDA-approved immune checkpoint inhibitors. Therefore, targeting the LAG-3/FGL1 pathway represents a promising therapeutic strategy to maximize the number of patients benefiting from checkpoint blockade therapy. However, there are no small molecules in existence that target LAG-3/FGL1 interaction. Herein, we report a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate the ability of small molecules to inhibit LAG-3/FGL1 interaction. We further demonstrate the implementation of the developed assay in screening chemical libraries of small molecules from the NCI Diversity Set VII, FDA-approved drugs, and a focused library of NF-κB modulators. This work will pave the way for drug discovery efforts focused on therapeutic targeting of LAG-3/FGL1 interaction using small molecules.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 4","pages":"Pages 188-192"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598839","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}
SLAS DiscoveryPub Date : 2023-06-01DOI: 10.1016/j.slasd.2023.03.002
Michaela Feodoroff , Piia Mikkonen , Laura Turunen , Antti Hassinen , Lauri Paasonen , Lassi Paavolainen , Swapnil Potdar , Astrid Murumägi , Olli Kallioniemi , Vilja Pietiäinen
{"title":"Comparison of two supporting matrices for patient-derived cancer cells in 3D drug sensitivity and resistance testing assay (3D-DSRT)","authors":"Michaela Feodoroff , Piia Mikkonen , Laura Turunen , Antti Hassinen , Lauri Paasonen , Lassi Paavolainen , Swapnil Potdar , Astrid Murumägi , Olli Kallioniemi , Vilja Pietiäinen","doi":"10.1016/j.slasd.2023.03.002","DOIUrl":"10.1016/j.slasd.2023.03.002","url":null,"abstract":"<div><p>Central to the success of functional precision medicine of solid tumors is to perform drug testing of patient-derived cancer cells (PDCs) in tumor-mimicking <em>ex vivo</em> conditions. While high throughput (HT) drug screening methods have been well-established for cells cultured in two-dimensional (2D) format, this approach may have limited value in predicting clinical responses. Here, we describe the results of the optimization of drug sensitivity and resistance testing (DSRT) in three-dimensional (3D) growth supporting matrices in a HT mode (3D-DSRT) using the hepatocyte cell line (HepG2) as an example. Supporting matrices included widely used animal-derived Matrigel and cellulose-based hydrogel, GrowDex, which has earlier been shown to support 3D growth of cell lines and stem cells. Further, the sensitivity of ovarian cancer PDCs, from two patients included in the functional precision medicine study, was tested for 52 drugs in 5 different concentrations using 3D-DSRT.</p><p>Shortly, in the optimized protocol, the PDCs are embedded with matrices and seeded to 384-well plates to allow the formation of the spheroids prior to the addition of drugs in nanoliter volumes with acoustic dispenser. The sensitivity of spheroids to drug treatments is measured with cell viability readout (here, 72 h after addition of drugs). The quality control and data analysis are performed with openly available Breeze software. We show the usability of both matrices in established 3D-DSRT, and report 2D vs 3D growth condition dependent differences in sensitivities of ovarian cancer PDCs to MEK-inhibitors and cytotoxic drugs. This study provides a proof-of-concept for robust and fast screening of drug sensitivities of PDCs in 3D-DSRT, which is important not only for drug discovery but also for personalized <em>ex vivo</em> drug testing in functional precision medicine studies. These findings suggest that comparing results of 2D- and 3D-DSRT is essential for understanding drug mechanisms and for selecting the most effective treatment for the patient.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 4","pages":"Pages 138-148"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9592481","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}
SLAS DiscoveryPub Date : 2023-06-01DOI: 10.1016/j.slasd.2023.04.002
Sarah Bitzer , Mozhgan Dehghan Harati , Karim C. El Kasmi , Daniela Schloesser , Julia Sauer , Heiko Olbrich , Michael Schuler , Florian Gantner , Ralf Heilker
{"title":"Application of human iPSC-derived macrophages in a miniaturized high-content-imaging-based efferocytosis assay","authors":"Sarah Bitzer , Mozhgan Dehghan Harati , Karim C. El Kasmi , Daniela Schloesser , Julia Sauer , Heiko Olbrich , Michael Schuler , Florian Gantner , Ralf Heilker","doi":"10.1016/j.slasd.2023.04.002","DOIUrl":"10.1016/j.slasd.2023.04.002","url":null,"abstract":"<div><p>Macrophages play a pivotal role in drug discovery due to their key regulatory functions in health and disease. Overcoming the limited availability and donor variability of human monocyte-derived macrophages (MDMs), human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) could provide a promising tool for both disease modeling and drug discovery. To access large numbers of model cells for medium- to high-throughput application purposes, an upscaled protocol was established for differentiation of iPSCs into progenitor cells and subsequent maturation into functional macrophages. These IDM cells resembled MDMs both with respect to surface marker expression and phago- as well as efferocytotic function. A statistically robust high-content-imaging assay was developed to quantify the efferocytosis rate of IDMs and MDMs allowing for measurements both in the 384- and 1536-well microplate format. Validating the applicability of the assay, inhibitors of spleen tyrosine kinase (Syk) were shown to modulate efferocytosis in IDMs and MDMs with comparable pharmacology. The miniaturized cellular assay with the upscaled provision of macrophages opens new routes to pharmaceutical drug discovery in the context of efferocytosis-modulating substances.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 4","pages":"Pages 149-162"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9973223","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}
SLAS DiscoveryPub Date : 2023-06-01DOI: 10.1016/j.slasd.2023.04.004
Emma J. Chory , Meng Wang , Michele Ceribelli , Aleksandra M Michalowska , Stefan Golas , Erin Beck , Carleen Klumpp-Thomas , Lu Chen , Crystal McKnight , Zina Itkin , Kelli M. Wilson , David Holland , Sanjay Divakaran , James Bradner , Javed Khan , Berkley E. Gryder , Craig J. Thomas , Benjamin Z. Stanton
{"title":"High-throughput approaches to uncover synergistic drug combinations in leukemia","authors":"Emma J. Chory , Meng Wang , Michele Ceribelli , Aleksandra M Michalowska , Stefan Golas , Erin Beck , Carleen Klumpp-Thomas , Lu Chen , Crystal McKnight , Zina Itkin , Kelli M. Wilson , David Holland , Sanjay Divakaran , James Bradner , Javed Khan , Berkley E. Gryder , Craig J. Thomas , Benjamin Z. Stanton","doi":"10.1016/j.slasd.2023.04.004","DOIUrl":"10.1016/j.slasd.2023.04.004","url":null,"abstract":"<div><p>We report a comprehensive drug synergy study in acute myeloid leukemia (AML). In this work, we investigate a panel of cell lines spanning both MLL-rearranged and non-rearranged subtypes. The work comprises a resource for the community, with many synergistic drug combinations that could not have been predicted <em>a priori</em>, and open source code for automation and analyses<em>.</em> We base our definitions of drug synergy on the Chou-Talalay method, which is useful for visualizations of synergy experiments in isobolograms, and median-effects plots, among other representations. Our key findings include drug synergies affecting the chromatin state, specifically in the context of regulation of the modification state of histone H3 lysine-27. We report open source high throughput methodology such that multidimensional drug screening can be accomplished with equipment that is accessible to most laboratories. This study will enable preclinical investigation of new drug combinations in a lethal blood cancer, with data analysis and automation workflows freely available to the community.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 4","pages":"Pages 193-201"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10089822","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}
SLAS DiscoveryPub Date : 2023-06-01DOI: 10.1016/j.slasd.2023.03.006
Sang-Yun Lee , In-Seong Koo , Hyun Ju Hwang , Dong Woo Lee
{"title":"In Vitro three-dimensional (3D) cell culture tools for spheroid and organoid models","authors":"Sang-Yun Lee , In-Seong Koo , Hyun Ju Hwang , Dong Woo Lee","doi":"10.1016/j.slasd.2023.03.006","DOIUrl":"10.1016/j.slasd.2023.03.006","url":null,"abstract":"<div><p>Three-dimensional (3D) cell culture technology has been steadily studied since the 1990′s due to its superior biocompatibility compared to the conventional two-dimensional (2D) cell culture technology, and has recently developed into an organoid culture technology that further improved biocompatibility. Since the 3D culture of human cell lines in artificial scaffolds was demonstrated in the early 90′s, 3D cell culture technology has been actively developed owing to various needs in the areas of disease research, precision medicine, new drug development, and some of these technologies have been commercialized. In particular, 3D cell culture technology is actively being applied and utilized in drug development and cancer-related precision medicine research. Drug development is a long and expensive process that involves multiple steps—from target identification to lead discovery and optimization, preclinical studies, and clinical trials for approval for clinical use. Cancer ranks first among life-threatening diseases owing to intra-tumoral heterogeneity associated with metastasis, recurrence, and treatment resistance, ultimately contributing to treatment failure and adverse prognoses. Therefore, there is an urgent need for the development of efficient drugs using 3D cell culture techniques that can closely mimic <em>in vivo</em> cellular environments and customized tumor models that faithfully represent the tumor heterogeneity of individual patients. This review discusses 3D cell culture technology focusing on research trends, commercialization status, and expected effects developed until recently. We aim to summarize the great potential of 3D cell culture technology and contribute to expanding the base of this technology.</p></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"28 4","pages":"Pages 119-137"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9600340","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}