CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption.
CL 277,082 (I) was found to be a potent inhibitor of acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in microsomes from a variety of tissues with IC50 values of 0.14 microM for intestinal mucosal microsomes, 0.74 microM for liver, and 1.18 microM for rat adrenal. I was also shown to inhibit...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1989-05-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520383280 |
| _version_ | 1818862435014017024 |
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| author | E E Largis C H Wang V G DeVries S A Schaffer |
| author_facet | E E Largis C H Wang V G DeVries S A Schaffer |
| author_sort | E E Largis |
| collection | DOAJ |
| description | CL 277,082 (I) was found to be a potent inhibitor of acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in microsomes from a variety of tissues with IC50 values of 0.14 microM for intestinal mucosal microsomes, 0.74 microM for liver, and 1.18 microM for rat adrenal. I was also shown to inhibit ACAT in cultured smooth muscle cells (IC50 = 0.8 microM) and was found to be specific in inhibiting cholesterol esterification since it did not inhibit fatty acid incorporation into triglycerides or phospholipids. Also, other cholesterol esterifying enzymes such as lecithin:cholesterol acyltransferase (LCAT) and pancreatic cholesterol esterase were not inhibited by I, nor was esterification of retinol by acyl CoA:retinol acyltransferase (ARAT) from intestinal mucosal microsomes inhibited. I was a potent inhibitor of cholesterol absorption in cholesterol-fed rats by markedly inhibiting increases in liver and serum cholesterol concentration (ED50 = 5.2 mg/kg per day) while increasing the excretion of neutral 14C-labeled sterol in the feces. |
| first_indexed | 2024-12-19T09:59:49Z |
| format | Article |
| id | doaj.art-f2c77325ffa74ed1b6d1a84ef2965cc6 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T09:59:49Z |
| publishDate | 1989-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-f2c77325ffa74ed1b6d1a84ef2965cc62022-12-21T20:26:42ZengElsevierJournal of Lipid Research0022-22751989-05-01305681690CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption.E E Largis0C H Wang1V G DeVries2S A Schaffer3American Cyanamid Company, Medical Research Division, Pearl River, NY 10965.American Cyanamid Company, Medical Research Division, Pearl River, NY 10965.American Cyanamid Company, Medical Research Division, Pearl River, NY 10965.American Cyanamid Company, Medical Research Division, Pearl River, NY 10965.CL 277,082 (I) was found to be a potent inhibitor of acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in microsomes from a variety of tissues with IC50 values of 0.14 microM for intestinal mucosal microsomes, 0.74 microM for liver, and 1.18 microM for rat adrenal. I was also shown to inhibit ACAT in cultured smooth muscle cells (IC50 = 0.8 microM) and was found to be specific in inhibiting cholesterol esterification since it did not inhibit fatty acid incorporation into triglycerides or phospholipids. Also, other cholesterol esterifying enzymes such as lecithin:cholesterol acyltransferase (LCAT) and pancreatic cholesterol esterase were not inhibited by I, nor was esterification of retinol by acyl CoA:retinol acyltransferase (ARAT) from intestinal mucosal microsomes inhibited. I was a potent inhibitor of cholesterol absorption in cholesterol-fed rats by markedly inhibiting increases in liver and serum cholesterol concentration (ED50 = 5.2 mg/kg per day) while increasing the excretion of neutral 14C-labeled sterol in the feces.http://www.sciencedirect.com/science/article/pii/S0022227520383280 |
| spellingShingle | E E Largis C H Wang V G DeVries S A Schaffer CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. Journal of Lipid Research |
| title | CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. |
| title_full | CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. |
| title_fullStr | CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. |
| title_full_unstemmed | CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. |
| title_short | CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. |
| title_sort | cl 277 082 a novel inhibitor of acat catalyzed cholesterol esterification and cholesterol absorption |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520383280 |
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