The ability of CH-223191 to compete with TCDD for binding to the AhR was assessed by incubating aliquots of cytosol prepared from untreated Hepa cells (2.1–2.5 mg protein/ml) with CH-223191 or flavone and [3H]TCDD at 3 nM for 2 h at room temperature. This concentration of TCDD is nonsaturating at these protein concentrations. Specific binding of [3H]TCDD was determined in duplicate aliquots by the hydroxylapatite assay(Gasiewicz and Neal, 1982), with correction for nonspecific binding measured in the presence of 150-fold excess of unlabeled 2,3,7,8-tetrachlorodibenzofuran. Data were expressed for each antagonist concentration as a percentage of the specific binding of [3H]TCDD in the absence of competitor.[1]
SMILES
O=C(C1=CC=NN1C)NC2=CC=C(/N=N/C3=CC=CC=C3C)C=C2C
靶点
Aryl Hydrocarbon Receptor(AhR)
动物实验
Male ICR mice (6 weeks old) were given oral vehicle (corn oil) or CH-223191 (10 mg/kg in corn oil) once a day for 25 days and treated i.p. with TCDD (100 g/kg in corn oil) once after the first week of CH-223191 treatment. The body weights of all mice were measured before dosing and at termination.[1]
数据来源文献
[1] Kim SH, et al. Mol Pharmacol. 2006, 69(6), 1871-1878. [2] Gramatzki D, et al. Oncogene. 2009, 28(28), 2593-2605. [3] Xie HQ, et al. Environ Health Perspect. 2013, 121(5), 613-618. [4] de Souza AR, et al. Toxicol Sci. 2014, 140(1), 204-223.