دورية أكاديمية
High-content phenotypic screening and triaging strategy to identify small molecules driving oligodendrocyte progenitor cell differentiation.
| العنوان: | High-content phenotypic screening and triaging strategy to identify small molecules driving oligodendrocyte progenitor cell differentiation. |
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| المؤلفون: | Peppard JV; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., Rugg CA; Lead Generation & Candidate Realization, Sanofi R&D, Bridgewater, NJ, USA., Smicker MA; Information Services, Genzyme, Framingham, MA, USA., Powers E; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., Harnish E; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., Prisco J; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., Cirovic D; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., Wright PS; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., August PR; Lead Generation & Candidate Realization, Sanofi Tucson Innovation Center, Tucson, AZ, USA., Chandross KJ; MS and Neurology Clinical, Sanofi-Genzyme, Bridgewater, NJ, USA Karen.chandross@sanofi.com. |
| المصدر: | Journal of biomolecular screening [J Biomol Screen] 2015 Mar; Vol. 20 (3), pp. 382-90. Date of Electronic Publication: 2014 Nov 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Sage Publications Country of Publication: United States NLM ID: 9612112 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-454X (Electronic) Linking ISSN: 10870571 NLM ISO Abbreviation: J Biomol Screen Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2004- > : Thousand Oaks, CA : Sage Publications Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c1996- |
| مواضيع طبية MeSH: | Drug Evaluation, Preclinical* , High-Throughput Screening Assays* , Phenotype* , Small Molecule Libraries*, Cell Differentiation/*drug effects , Neural Stem Cells/*cytology , Neural Stem Cells/*drug effects , Oligodendroglia/*cytology , Oligodendroglia/*drug effects, Animals ; Cell Line ; Drug Discovery ; Humans ; Multiple Sclerosis ; Neural Stem Cells/metabolism ; Rats ; Reproducibility of Results ; Sensitivity and Specificity |
| مستخلص: | Multiple Sclerosis is a demyelinating disease of the CNS and the primary cause of neurological disability in young adults. Loss of myelinating oligodendrocytes leads to neuronal dysfunction and death and is an important contributing factor to this disease. Endogenous oligodendrocyte precursor cells (OPCs), which on differentiation are responsible for replacing myelin, are present in the adult CNS. As such, therapeutic agents that can stimulate OPCs to differentiate and remyelinate demyelinated axons under pathologic conditions may improve neuronal function and clinical outcome. We describe the details of an automated, cell-based, morphometric-based, high-content screen that is used to identify small molecules eliciting the differentiation of OPCs after 3 days. Primary screening was performed using rat CG-4 cells maintained in culture conditions that normally support a progenitor cell-like state. From a library of 73,000 diverse small molecules within the Sanofi collection, 342 compounds were identified that increased OPC morphological complexity as an indicator of oligodendrocyte maturation. Subsequent to the primary high-content screen, a suite of cellular assays was established that identified 22 nontoxic compounds that selectively stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This rigorous triaging yielded several chemical series for further expansion and bio- or cheminformatics studies, and their compelling biological activity merits further investigation. (© 2014 Society for Laboratory Automation and Screening.) |
| فهرسة مساهمة: | Keywords: CNS repair; Multiple Sclerosis (MS); high-content screening (HCS); oligodendrocyte progenitor cell (OPC); phenotypic screening; remyelination |
| المشرفين على المادة: | 0 (Small Molecule Libraries) |
| تواريخ الأحداث: | Date Created: 20141115 Date Completed: 20151120 Latest Revision: 20150221 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1177/1087057114559490 |
| PMID: | 25394729 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1552-454X |
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| DOI: | 10.1177/1087057114559490 |