دورية أكاديمية
High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase.
| العنوان: | High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase. |
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| المؤلفون: | Aseeri M; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain., Abad JL; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain., Delgado A; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.; Department of Pharmacology, Toxicology and Medicinal Chemistry, Unit of Pharmaceutical Chemistry (Associated Unit to CSIC), Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain., Fabriàs G; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.; Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), ISCIII, Madrid, Spain., Triola G; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain., Casas J; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.; Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), ISCIII, Madrid, Spain. |
| المصدر: | Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2023 Dec; Vol. 38 (1), pp. 343-348. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 101150203 Publication Model: Print Cited Medium: Internet ISSN: 1475-6374 (Electronic) Linking ISSN: 14756366 NLM ISO Abbreviation: J Enzyme Inhib Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basingstoke, UK : Taylor & Francis, c2002- |
| مواضيع طبية MeSH: | Acid Ceramidase*/antagonists & inhibitors , Neoplasms*, Humans ; Apoptosis ; Ceramides/chemistry ; Small Molecule Libraries |
| مستخلص: | Ceramide has a key role in the regulation of cellular senescence and apoptosis. As Ceramide levels are lowered by the action of acid ceramidase (AC), abnormally expressed in various cancers, the identification of AC inhibitors has attracted increasing interest. However, this finding has been mainly hampered by the lack of formats suitable for the screening of large libraries. We have overcome this drawback by adapting a fluorogenic assay to a 384-well plate format. The performance of this optimised platform has been proven by the screening a library of 4100 compounds. Our results show that the miniaturised platform is well suited for screening purposes and it led to the identification of several hits, that belong to different chemical classes and display potency ranges of 2-25 µM. The inhibitors also show selectivity over neutral ceramidase and retain activity in cells and can therefore serve as a basis for further chemical optimisation. |
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| فهرسة مساهمة: | Keywords: Sphingolipids; acid ceramidase; ceramide; inhibitor |
| المشرفين على المادة: | EC 3.5.1.23 (Acid Ceramidase) 0 (Ceramides) 0 (Small Molecule Libraries) |
| تواريخ الأحداث: | Date Created: 20221215 Date Completed: 20221219 Latest Revision: 20221222 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9762759 |
| DOI: | 10.1080/14756366.2022.2150183 |
| PMID: | 36519337 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1475-6374 |
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| DOI: | 10.1080/14756366.2022.2150183 |