Candesartan (CV 11974) is an angiotensin II receptor blocker used widely in the therapy of hypertension and heart failure.

AT1 receptor:0.26 nM

在处理携带KU-19-19移植瘤的小鼠中,Candesartan（10 mg/kg）能够降低微血管密度和VEGF的表达,抑制肿瘤细胞生长.在WKY大鼠中,Candesartan（0.5 mg/kg ）能够降低血压,抑制AT1在穹窿下器,下丘脑室旁核,孤束核,和极后区的结合.在成年自发性高血压大鼠中,Candesartan（0.3 mg/kg）能够减少梗死区域,减少在缺血周边区域和皮层下严重缺血性病变区域,减低脑部血流量的减少.

在CHO-AT1细胞中,Candesartan 能够高选择性地与血管紧张素II AT1 受体结合。Candesartan（0.1 nM）能够降低对于血管紧张素II的最大收缩反应。在 KU-19-19细胞中,加入Candesartan,能够上调VEGF和和白细胞介素-8的表达,同时不影响细胞增殖。

Binding assay: Cells are plated in 24-well plates and cultured until confluence. Before the experiment, the cells are washed three times with 0.5 mL per well of DMEM at room temperature. After removal of the medium, 400 μL binding DMEM is added and the plate is then left for 15 min at 37 ℃. For saturation binding assays cells are incubated with increasing concentrations [3H]Candesartan (final concentrations between 0.15 nM and 15 nM) in a final volume of 0.5 mL at 37 ℃ for 5 min to 180 min. For competition binding assays 50 μL of buffer or 50 μL of buffer containing increasing concentrations of unlabelled Candesartan is added. After 30 min, 50 μL of buffer containing [3H]Candesartan (final concentration 1.1 nM) or [3H]Candesartan (final concentration 1.0 nM) is added, and the cells are further incubated for 30 min at 37 ℃.

KU-19-19 cells are seeded at a cell density of 2 × 104 per well in 96-well plates and allowed to grow overnight. Then the cells are treated with various concentrations of Candesartan for various periods of time. Cell viability is determined by the Alamar Blue assay to examine the cytotoxicity and antiproliferative effect of candesartan. The absorbance value of each well is determined in a microplate reade(Only for Reference)