Ambrisentan

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.

177036-94-1

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

Pharmacology & Drug Discovery

>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

C22H22N2O4

378.4211

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.