|S1456||Zibotentan (ZD4054)||<1 mg/mL||24 mg/mL||<1 mg/mL|
|S3051||Bosentan Hydrate||0.001 mg/mL||100 mg/mL||2 mg/mL|
|S8051||Macitentan||<1 mg/mL||100 mg/mL||<1 mg/mL|
|S2097||Ambrisentan||<1 mg/mL||76 mg/mL||22 mg/mL|
|S4220||Bosentan||<1 mg/mL||100 mg/mL||3 mg/mL|
|S7883||BQ-123||<1 mg/mL||100 mg/mL||15 mg/mL|
- Endothelin Receptor抑制剂（6）
Zibotentan (ZD4054)是一种特异性的Endothelin (ET)A拮抗剂，IC50为21 nM，对ETB没有抑制活性。Phase 3。
(E and F) Photomicrograph and quantifications showing reducing in inflammation in steatosis in IL27RA-/-p53H/1 mice treated with ZD4054 (N=9), when compared to sham treated mice (N=7). Chi-square test was used to determine the differences among these two groups. In vivo data with ZD4054 inhibitor was repeated twice with similar results. (i) WT, (ii) IL27RA-/-, (iii) p53H/1, or (iv) IL27RA-/-p53H/1. Dots indicate data from liver of individual mice. Pictures taken at 2003. *P < 0.05. Abbreviation: DAPI, 40,6-diamidino-2-phenylindole.
Bosentan Hydrate是一种内皮素(ET)受体拮抗剂，靶点有ET-A和ET-B，Ki分别为4.7 nM和95 nM。
Macitentan是一种口服有效的，非肽类，ETA/ETB(内皮素) receptor双重拮抗剂，IC50为0.5 nM/391 nM。
Bosentan 是一种 endothelin (ET) receptor 拮抗剂，其作用于 ET-A 和 ET-B 的 Ki分别为 4.7 nM 和 95 nM。
Effects of TGF-β1, or ET-1, or TGF-β1 plus ET-1 on α-SMA protein levels and Acta2 gene expression in cultured murine lung microvascular endothelial cells(A). α-SMA protein levels. The upper panel shows a Western blot of cell lysates from the same samples shown in Fig 1B probed with α-SMA (upper bands). GAPDH was used as loading control (lower bands). The Bottom panel shows a quantitative densitometry of α-SMA analyzed using NIH Image J software. (B). Acta2 expression. Expression levels of Acta2 determined by semiquantitative RT-PCR. Values represent the mean (+/- standard deviation) expression levels of three replicates of three separate experiments. C(t) values were normalized with Gapdh. The saline control levels were arbitrarily set at 100% expression. Values for other samples are expressed relative to the saline control. Statistical significance was determined by Student's two-tailed t test. ***: p<0.001.
BQ-123 是一种选择性 endothelin A receptor (ETA) 拮抗剂，IC50 为 7.3 nM。Phase 2。
Effects of 0.1% DMSO (as a vehicle), BQ-123 (a selective ETA receptor antagonist), BQ-788 (a selective ETB receptor antagonist), YM-254890 (a selective Gq protein inhibitor), PTX (a selective Gi protein inhibitor) and NF449 (a Gs protein inhibitor) on the ET-1-induced inhibition of insulinstimulated Akt phosphorylation in L6 myotubes. The cells were treated with 30 nM ET-1 for indicated times during treatment with 100 nM insulin for 60 min. The cells were treated with one of the drugs for 30 min (except PTX for 18 h) before treatment with 100 nM insulin for 60 min. (A) Representative immunoblots obtained using antibodies to phospho-Akt at Thr308 [p-Akt (T308)], phospho-Akt at Ser473 [p-Akt (S473)] and total Akt (t-Akt). (B) ET-1-induced changes in the ratio of phosphorylated Akt to t-Akt. Ordinate represents Akt phosphorylation responses, which are normalized to the level of insulin-stimulated Akt phosphorylation in L6 myotubes without treatment with ET-1, vehicle, antagonists or inhibitors. Data are presented as means ± SEM of the results obtained from five to six experiments. *P < 0.05 versus its control (100 nM insulin alone).