High-Throughput Screening for the Discovery of Inhibitors of Fatty Acid Amide Hydrolase Using a Microsome-Based Fluorescent Assay
| Autor: | Kathryn E. Rogers, Jun Xu, Manjunath K. Ramarao, Girija Krishnamurthy, Fernando Ramirez, Adam M. Gilbert, Gary Kalgaonkar, Wade Edris, Yuren Wang, Nina Kadakia, Philip G. Jones |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Oleamide
High-throughput screening Drug Evaluation Preclinical CHO Cells Transfection Models Biological Biochemistry Amidohydrolases Analytical Chemistry Automation Inhibitory Concentration 50 chemistry.chemical_compound Fatty acid amide hydrolase Cricetinae Microsomes Amide Animals Humans Enzyme Inhibitors Fluorescent Dyes chemistry.chemical_classification Chemistry Fatty acid Anandamide Enzyme nervous system Microsome Molecular Medicine lipids (amino acids peptides and proteins) Biotechnology |
| Zdroj: | SLAS Discovery. 11:519-527 |
| ISSN: | 2472-5552 |
| Popis: | Fatty acid amide hydrolase (FAAH) is a membrane-associated enzyme that catalyzes the hydrolysis of several endogenous bioactive lipids, including anandamide (AEA), N-palmitoylethanolamine (PEA), oleamide, and N-oleoylethanolamine (OEA). These fatty acid amides participate in many physiological activities such as analgesia, anxiety, sleep modulation, antiinflammatory responses, and appetite suppression. Because FAAH plays an essential role in controlling the tone and activity of these endogenous bioactive lipids, this enzyme has been implicated to be a drug target for the therapeutic management of pain, anxiety, and other disorders. In an effort to discover FAAH inhibitors, the authors have previously reported the development of a novel fluorescent assay using purified FAAH microsomes as an enzyme source and a fluorogenic substrate, arachidonyl 7-amino, 4-methyl coumarin amide (AAMCA). Herein, the authors have adapted this assay to a high-throughput format and have screened a large library of small organic compounds, identifying a number of novel FAAH inhibitors. These data further verify that this fluorescent assay is sufficiently robust, efficient, and low-cost for the identification of FAAH inhibitory molecules and open this class of enzymes for therapeutic exploration. (Journal of Biomolecular Screening 2006:519-527) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|