کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2514097 | 1118448 | 2008 | 10 صفحه PDF | دانلود رایگان |
The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor responsible for the recognition of potentially toxic endo- and exogenous compounds whose elimination from the body is accelerated by the CAR-mediated inducible expression of metabolizing enzymes and transporters. Despite the importance of CAR, few human agonists are known so far. Following a sequential virtual screening procedure using a 3D pharmacophore and molecular docking approach, we identified 17 novel agonists that could activate human CAR in vitro and enhance its association with the nuclear receptor co-activator SRC1. Selected agonists also increased the expression of the human CAR target CYP2B6 mRNA in primary hepatocytes. Composed of substituted sulfonamides and thiazolidin-4-one derivatives, these agonists represent two novel chemotypes capable of human CAR activation, thus broadening the agonist spectrum of CAR.
Journal: Biochemical Pharmacology - Volume 76, Issue 10, 15 November 2008, Pages 1288–1297