product name Ambrisentan
Description: Ambrisentan, also known as BSF-208075 and LU-208075, is a highly selective antagonist of the endothelin-1 type A receptor. Ambrisentanis a drug used for the treatment of pulmonary hypertension. Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2). Ambrisentan was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency, and designated an orphan drug, for the treatment of pulmonary hypertension.
References: Biol Pharm Bull. 2014;37(3):461-5; Biochem Pharmacol. 2013 Jan 15;85(2):265-73.
378.42
Formula
C22H22N2O4
CAS No.
177036-94-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 76 mg/mL (200.8 mM)
Water: <1 mg/mL
Ethanol: 22 mg/mL (58.1 mM)
Solubility (In vivo)
Synonyms
LU-208075,BSF-208075
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19417217
| In Vitro |
In vitro activity: Ambrisentan only increases intracellular calcein fluorescence in P388/dx cells at concentrations above 100 μM and in L-MDR1 cells not at all indicating negligible P-gp inhibition. Ambrisentan inhibits specific [(125)I]ET-1 binding in these tissues in a concentration-dependent manner. Ambrisentan undergoes oxidative metabolism mainly by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP3A5 and CYP2C19. Ambrisentan is not only a strong inducer of CYP3A4, but also of ABCB1 and ABCG2. Ambrisentan also has a concentration-dependent effect on PXR activity, but because plateau effects are not reached, an EC50-value could not be calculated. Ambrisentan inhibits specific [(125)I]ET-1 binding in a concentration-dependent manner at nanomolar ranges of IC50. Ambrisentan significantly increases the dissociation constant for bladder [(125)I]ET-1 binding without affecting maximal number of binding sites (Bmax). Ambrisentan seem to bind to bladder ET-1 receptor in a competitive and reversible manner. Ambrisentan is an effective and safe treatment which is a valuable addition to the armamentarium against PAH. Ambrisentan offers a relative lack of drug interactions, once daily dosing and reassuring liver safety, offering safety and convenience advantages over bosentan. Kinase Assay: Cell Assay: |
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| References | Biol Pharm Bull. 2014;37(3):461-5; Biochem Pharmacol. 2013 Jan 15;85(2):265-73. |
