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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H22N2O4
Molecular Weight 378.4211
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMBRISENTAN

SMILES

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

InChI

InChIKey=OUJTZYPIHDYQMC-LJQANCHMSA-N
InChI=1S/C22H22N2O4/c1-15-14-16(2)24-21(23-15)28-19(20(25)26)22(27-3,17-10-6-4-7-11-17)18-12-8-5-9-13-18/h4-14,19H,1-3H3,(H,25,26)/t19-/m1/s1

HIDE SMILES / InChI

Description

Ambrisentan (alternative Names: BSF 208075; GSK 1325760; GSK1325760A; Letairis) is an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor. The chemical name of ambrisentan is (+)-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid. Ambrisentan is indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. As an endothelin receptor antagonist, ambrisentan prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure. Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance. In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries. These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH. Ambrisentan is a high-affinity (Ki=0.011 nM) ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor (>4000-fold). The clinical impact of high selectivity for ETA is not known.

Originator

Approval Year

Targets

Targets

Conditions
PubMed

PubMed

TitleDatePubMed
Drug Insight: endothelin-receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases.
2005 Dec
Ambrisentan for pulmonary arterial hypertension.
2005 Jul
Endothelin receptor antagonism in pulmonary arterial hypertension--a role for selective ET(A) inhibition?
2006 Dec
[Treatment of pulmonary arterial hypertension: endothelin-receptor antagonists].
2006 Dec 8
Gateways to clinical trials.
2006 Jan-Feb
Endothelin antagonism prevents diabetic retinopathy in NOD mice: a potential role of the angiogenic factor adrenomedullin.
2006 Jun
Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug.
2006 Jun
[Pulmonary hypertension and right ventricular failure. Part XI. Endothelin receptor blockers in the treatment of primary pulmonary arterial hypertension].
2007
Review of bosentan in the management of pulmonary arterial hypertension.
2007
Therapeutic targets in systemic sclerosis.
2007
A review of pulmonary arterial hypertension: role of ambrisentan.
2007
Gateways to clinical trials.
2007 Apr
EndothelinA receptor antagonist BSF-208075 causes immune modulation and neuroprotection after stroke in gerbils.
2007 Jul 9
Gateways to clinical trials.
2007 Mar
Endothelin receptor antagonists in the treatment of pulmonary arterial hypertension.
2007 Mar
Pathophysiological role of platelets in acute experimental pancreatitis: influence of endothelin A receptor blockade.
2007 Mar
Ambrisentan (Letairis) for pulmonary arterial hypertension.
2007 Oct 22
Ambrisentan.
2007 Sep
Ambrisentan.
2008
[Treatment of pulmonary arterial hypertension by endothelin receptor antagonists in 2008].
2008 Apr
[Current treatment of systemic sclerosis. Part II. Vascular and antifibrotic treatment].
2008 Aug
Acute right ventricular failure in the setting of acute pulmonary embolism or chronic pulmonary hypertension: a detailed review of the pathophysiology, diagnosis, and management.
2008 Feb
Pulmonary hypertension: past, present and future.
2008 Jan
The status of pulmonary arterial hypertension in 2008.
2008 Jun 10
Gateways to clinical trials.
2008 Mar
The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house?
2008 Mar
Ambrisentan for the management of pulmonary arterial hypertension.
2008 May
Therapeutic methods used in patients with Eisenmenger syndrome.
2009
Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model.
2009
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient.
2009
Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis.
2009
Treatment of pediatric pulmonary hypertension.
2009
Endothelin-1 inhibition by ambrisentan as a potential treatment adjunct after debulking surgery in epithelial ovarian cancer.
2009
[Pulmonary arterial hypertension: a voyage around the year 2008].
2009
Ambrisentan: new drug. Too risky in mildly symptomatic pulmonary hypertension.
2009 Apr
Use of inhaled iloprost in an infant with bronchopulmonary dysplasia and pulmonary artery hypertension.
2009 Aug
Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension.
2009 Aug
[Endothelin receptor antagonists - their role in pulmonary medicine].
2009 Dec
Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease.
2009 Dec
A meta-analysis of randomized controlled trials in pulmonary arterial hypertension.
2009 Feb
Ambrisentan for the treatment of pulmonary arterial hypertension.
2009 Feb 6
Gateways to clinical trials.
2009 Jun
Small-molecule endothelin receptor antagonists: a review of patenting activity across therapeutic areas.
2009 Jun
The pharmacokinetics and pharmacodynamics of warfarin in combination with ambrisentan in healthy volunteers.
2009 May
Gateways to clinical trials.
2009 Nov
Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension.
2009 Nov 17
Gateways to clinical trials.
2009 Sep
Can we improve outcome of congenital diaphragmatic hernia?
2009 Sep
Safety and tolerability of bosentan in the management of pulmonary arterial hypertension.
2009 Sep 21
Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis.
2010 Jan 29
Patents

Sample Use Guides

In Vivo Use Guide
5 mg once daily, and consider increasing the dose to 10 mg once daily if 5 mg is tolerated. Tablets may be administered with or without food.
Route of Administration: Oral
In Vitro Use Guide
The effect of the novel and ET(A) receptor selective antagonist LU 208075 (AMBRISENTAN) was characterized by the contraction and relaxation induced by ET-1 and bigET-1 on rat basilar artery. Concentration-effect curves were constructed by cumulative application of ET-1 or bigET-1 in the presence of LU 208075 (10(-7)M, 10(-6)M, and 10(-5)M). The effect of LU 208075 was determined by the pA(2) value. The contraction by ET-1 and bigET-1 was inhibited by LU 208075 in a dose-dependent manner.
Name Type Language
AMBRISENTAN
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
AMBRISENTAN [MI]
Common Name English
(+)-(2S)-2-((4,6-DIMETHYLPYRIMIDIN-2-YL)OXY)-3-METHOXY-3,3-DIPHENYLPROPANOIC ACID
Systematic Name English
AMBRISENTAN [JAN]
Common Name English
GSK1325760
Code English
AMBRISENTAN [ORANGE BOOK]
Common Name English
GSK-1325760
Code English
LU-208075
Code English
LETAIRIS
Brand Name English
VOLIBRIS
Brand Name English
AMBRISENTAN [MART.]
Common Name English
GSK1325760A
Code English
AMBRISENTAN [WHO-DD]
Common Name English
AMBRISENTAN [INN]
Common Name English
AMBRISENTAN [EMA EPAR]
Common Name English
GSK-1325760A
Code English
AMBRISENTAN [VANDF]
Common Name English
AMBRISENTAN, (+)-
Common Name English
Classification Tree Code System Code
WHO-ATC C02KX52
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
LIVERTOX 35
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
WHO-VATC QC02KX02
Created by admin on Mon Oct 21 20:44:26 UTC 2019 , Edited by admin on Mon Oct 21 20:44:26 UTC 2019
WHO-ATC C02KX02
Created by admin on Mon Oct 21 20:44:26 UTC 2019 , Edited by admin on Mon Oct 21 20:44:26 UTC 2019
EMA ASSESSMENT REPORTS VOLIBRIS (AUTHORIZED: HYPERTENSION, PULMONARY)
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
NCI_THESAURUS C270
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
EU-Orphan Drug EU/3/05/273
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
NDF-RT N0000175581
Created by admin on Mon Oct 21 20:44:26 UTC 2019 , Edited by admin on Mon Oct 21 20:44:26 UTC 2019
NDF-RT N0000175364
Created by admin on Mon Oct 21 20:44:26 UTC 2019 , Edited by admin on Mon Oct 21 20:44:26 UTC 2019
Code System Code Type Description
MERCK INDEX
M1648
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY Merck Index
RXCUI
358274
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY RxNorm
CAS
177036-94-1
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
PUBCHEM
6918493
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
ChEMBL
CHEMBL1111
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
IUPHAR
3951
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
DRUG BANK
DB06403
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
NCI_THESAURUS
C72694
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
EPA CompTox
177036-94-1
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
MESH
C467894
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
INN
8128
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY
EVMPD
SUB25424
Created by admin on Mon Oct 21 20:44:27 UTC 2019 , Edited by admin on Mon Oct 21 20:44:27 UTC 2019
PRIMARY