Ambrisentan

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Ambrisentan (BSF 208075;LU 208075) 是一种高度选择性的内皮素-1 A 型受体 (ETA) 拮抗剂，用于治疗肺动脉高压。

Ambrisentan (BSF 208075;LU 208075) is a highly selective antagonist of the endothelin-1 type A receptor (ETA) for use in the treatment of pulmonary hypertension.Hypertension Approved(In Vitro):Ambrisentan is an endothelin type A receptor antagonist. Ambrisentan induces Nrf2 activation. Endothelial permeability increased in BMEC monolayers at 24 h of hypoxia exposure and compared to vehicle control, Ambrisentan attenuates hypoxia-induced BMEC leak. These results are reversed when prior to treatment BMEC are transfected with siRNA against Nrf2. (In Vivo):In the Ambrisentan group, hepatic hydroxyproline content is significantly lower than in the control group (18.0 μg/g±6.1 μg/g vs 33.9 μg/g±13.5 μg/g liver, respectively, P=0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, are also significantly lower in the Ambrisentan group (0.46%±0.18% vs 1.11%±0.28%, respectively, P=0.0003; and 0.12%±0.08% vs 0.25%±0.11%, respectively, P=0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly lower by 60% and 45%, respectively, in the Ambrisentan group. Inflammation, steatosis, and endothelin-related mRNA expression in the liver are not significantly different between the groups. Ambrisentan attenuates the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.

Ambrisentan is an endothelin type A receptor antagonist. Ambrisentan induces Nrf2 activation. Endothelial permeability increased in BMEC monolayers at 24 h of hypoxia exposure and compared to vehicle control, Ambrisentan attenuates hypoxia-induced BMEC leak. These results are reversed when prior to treatment BMEC are transfected with siRNA against Nrf2.

In the Ambrisentan group, hepatic hydroxyproline content is significantly lower than in the control group (18.0 μg/g±6.1 μg/g vs 33.9 μg/g±13.5 μg/g liver, respectively, P=0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, are also significantly lower in the Ambrisentan group (0.46%±0.18% vs 1.11%±0.28%, respectively, P=0.0003; and 0.12%±0.08% vs 0.25%±0.11%, respectively, P=0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly lower by 60% and 45%, respectively, in the Ambrisentan group. Inflammation, steatosis, and endothelin-related mRNA expression in the liver are not significantly different between the groups. Ambrisentan attenuates the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.

BSF 208075 | LU 208075 | BSF208075 | BSF-208075 | LU208075 | LU-208075

GPCR/G Protein

Endothelin Receptor

ET-A

Cardiovascular Disease

Hypertension

177036-94-1

378.4211

C22H22N2O4

>98% (HPLC)

10 mM in DMSO

O=C(O)[C@@H](OC1=NC(C)=CC(C)=N1)C(C2=CC=CC=C2)(OC)C3=CC=CC=C3

Benzenepropanoic acid, .alpha.-[(4,6-dimethyl-2-pyrimidinyl)oxy]-.beta.-methoxy-.beta.-phenyl-, (.alpha.S)-

(-20℃)

With Ice Pack

≥ 2 years