AMBRISENTAN

Details

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

SHOW SMILES / InChI

Structure Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022081s029lbl.pdf

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

Primary Target	Pharmacology	Condition	Potency
Endothelin receptor ET-B 11 Target ID: CHEMBL1785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19920913	Antagonist 2737
Endothelin receptor ET-A 19 Target ID: CHEMBL252 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19920913	Antagonist 2737		0.011 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary arterial hypertension 35 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022081s029lbl.pdf	Primary		Approved 8307	LETAIRIS Approved Use Letairis is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): To improve exercise ability and delay clinical worsening. In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability [see Clinical Studies (14.2) Launch Date 1.18186561E12

C_max

Value	Dose	Co-administered	Analyte	Population
838.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19455620	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		AMBRISENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
6976.5 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19455620	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		AMBRISENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
18.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19455620	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		AMBRISENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022081s033lbl.pdf	steady-state, oral		AMBRISENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
10 mg 1 times / day multiple, oral Highest studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf https://pubmed.ncbi.nlm.nih.gov/22506623	unhealthy, 45.6 years n = 17 Health Status: unhealthy Condition: pulmonary arterial hypertension Age Group: 45.6 years Sex: M+F Population Size: 17 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf https://pubmed.ncbi.nlm.nih.gov/22506623	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf https://pubmed.ncbi.nlm.nih.gov/22506623
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf
5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf	pregnant, adult Health Status: pregnant Condition: pulmonary arterial hypertension Age Group: adult Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf	Other AEs: Fetal damage... Other AEs: Fetal damage (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf
5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf	unhealthy, adult Health Status: unhealthy Condition: pulmonary arterial hypertension Age Group: adult Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf	Other AEs: Liver injury... Other AEs: Liver injury (serious) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022081s000_LBL.pdf
5 mg 1 times / day multiple, oral (max) Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02080637	unhealthy, children n = 13 Health Status: unhealthy Condition: heart defects Age Group: children Population Size: 13 Sources: https://clinicaltrials.gov/ct2/show/NCT02080637	Other AEs: Anemia, Hypertension... Other AEs: Anemia (below serious, 2 patients) Hypertension (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02080637
10 mg 1 times / day steady, oral (max) Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00768300	unhealthy n = 329 Health Status: unhealthy Condition: Early Idiopathic Pulmonary Fibrosis Population Size: 329 Sources: https://clinicaltrials.gov/ct2/show/NCT00768300	Other AEs: Anaemia, Acute myocardial infarction... Other AEs: Anaemia (serious, 1 patient) Acute myocardial infarction (serious, 3 patients) Angina pectoris (serious, 1 patient) Angina unstable (serious, 1 patient) Atrial fibrillation (serious, 2 patients) Sinus tachycardia (serious, 1 patient) Cardiac failure congestive (serious, 4 patients) Cardiomegaly (serious, 1 patient) Dilatation atrial (serious, 1 patient) Tricuspid valve incompetence (serious, 1 patient) Palpitations (serious, 1 patient) Extrasystoles (serious, 1 patient) Electromechanical dissociation (serious, 1 patient) Acute vestibular syndrome (serious, 1 patient) Visual impairment (serious, 1 patient) Constipation (serious, 4 patients) Nausea (serious, 2 patients) Colonic polyp (serious, 1 patient) Small intestinal obstruction (serious, 1 patient) Upper gastrointestinal haemorrhage (serious, 1 patient) Oedema peripheral (serious, 4 patients) Oedema (serious, 1 patient) Pain (serious, 2 patients) Pyrexia (serious, 2 patients) Fatigue (serious, 2 patients) Catheter site haemorrhage (serious, 1 patient) Influenza like illness (serious, 1 patient) Hyperthermia (serious, 1 patient) Pharyngitis (serious, 1 patient) Sinusitis (serious, 1 patient) Pneumonia (serious, 9 patients) Bronchitis (serious, 3 patients) Bronchopneumonia (serious, 1 patient) Infection (serious, 1 patient) Cellulitis (serious, 2 patients) Sepsis (serious, 2 patients) Influenza (serious, 2 patients) Urinary tract infection (serious, 1 patient) Oral candidiasis (serious, 1 patient) Conjunctivitis viral (serious, 1 patient) Road traffic accident (serious, 1 patient) Fracture rib (serious, 1 patient) Electrocardiogram ST-T segment abnormal (serious, 1 patient) Electrocardiogram T wave inversion (serious, 1 patient) Computerised tomogram thorax abnormal (serious, 1 patient) Hyperkalaemia (serious, 4 patients) Hypokalaemia (serious, 2 patients) Hyperglycaemia (serious, 2 patients) Anorexia (serious, 1 patient) Diabetic ketoacidosis (serious, 1 patient) Hypophosphataemia (serious, 1 patient) Back pain (serious, 1 patient) Musculoskeletal pain (serious, 1 patient) Clubbing (serious, 1 patient) Pain in jaw (serious, 1 patient) Myalgia (serious, 1 patient) Squamous cell carcinoma (serious, 1 patient) Prostate cancer (serious, 1 patient) Prostate cancer metastatic (serious, 1 patient) Lung neoplasm malignant (serious, 1 patient) Headache (serious, 5 patients) Cerebrovascular accident (serious, 1 patient) Ischaemic stroke (serious, 1 patient) Somnolence (serious, 1 patient) Carotid artery stenosis (serious, 1 patient) Coma (serious, 1 patient) Grand mal convulsion (serious, 1 patient) Nerve compression (serious, 1 patient) Hypoaesthesia (serious, 1 patient) Anxiety (serious, 3 patients) Delirium (serious, 1 patient) Insomnia (serious, 1 patient) Renal failure acute (serious, 2 patients) Renal failure (serious, 1 patient) Benign prostatic hyperplasia (serious, 1 patient) Idiopathic pulmonary fibrosis (serious, 20 patients) Emphysema (serious, 2 patients) Pulmonary fibrosis (serious, 2 patients) Pulmonary alveolar haemorrhage (serious, 1 patient) Dyspnoea (serious, 17 patients) Respiratory arrest (serious, 1 patient) Cough (serious, 4 patients) Haemoptysis (serious, 4 patients) Productive cough (serious, 1 patient) Acute respiratory failure (serious, 5 patients) Respiratory failure (serious, 4 patients) Nasal congestion (serious, 4 patients) Allergic rhinitis (serious, 1 patient) Choking (serious, 1 patient) Rhinorrhoea (serious, 1 patient) Hypoxia (serious, 1 patient) Pneumothorax (serious, 1 patient) Pneumonitis (serious, 1 patient) Hiccups (serious, 1 patient) Pleurisy (serious, 1 patient) Hypotension (serious, 4 patients) Hypertension (serious, 3 patients) Subclavian vein thrombosis (serious, 1 patient) Flushing (serious, 1 patient) Hot flush (serious, 1 patient) Cardiac ventricular disorder (serious, 1 patient) Peripheral ischaemia (serious, 1 patient) Oedema peripheral (below serious, 73 patients) Upper respiratory tract infection (below serious, 47 patients) Headache (below serious, 47 patients) Dyspnoea (below serious, 40 patients) Nasopharyngitis (below serious, 37 patients) Idiopathic pulmonary fibrosis (below serious, 19 patients) Nasal congestion (below serious, 27 patients) Diarrhoea (below serious, 20 patients) Sinusitis (below serious, 20 patients) Back pain (below serious, 18 patients) Dizziness (below serious, 20 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00768300
10 mg 1 times / day steady, oral (max) Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02290613	unhealthy n = 19 Health Status: unhealthy Condition: Arterial Hypertension Population Size: 19 Sources: https://clinicaltrials.gov/ct2/show/NCT02290613	Other AEs: Jaw fracture, Edema... Other AEs: Jaw fracture (serious, 1 patient) Edema (below serious, 8 patients) Diarrhea (below serious, 4 patients) Paraesthesia (below serious, 4 patients) Epistaxis (below serious, 3 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT02290613

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670	inhibitor 1695

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 770 OATP1B3 691 NTCP 33 BSEP 392 BCRP 678 P-gp 1401 MRP2 363 CYP2A6 670 CYP2C8 869 UGT1A1 200 UGT1A6 107 UGT1A9 115 UGT2B7 145	P-gp 1491 CYP2C19 955 UGT1A9 378 UGT2B7 387 UGT1A3 421 OATP1B1 389 MRP2 196 BSEP 52 CYP3A5 383	NTCP 2 BSEP 6 MRP2 108

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 751	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022081s041lbl.pdf Page: 12.0	no
BSEP 393	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36.0	no
BSEP 393	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36.0	no
MRP2 452	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36.0	no
MRP2 452	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36.0	no
NTCP 34	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36.0	no
P-gp 1588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36, 61	no	no (co-administration study) Comment: ambrisentan had no inhibitory effect on the P-gp efflux of digoxin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36, 61
NTCP 34	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 36.0	weak [IC50 100 uM]
OATP1B3 700	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022081s041lbl.pdf Page: 12.0	weak [IC50 45 uM]
OATP1B1 785	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022081s041lbl.pdf Page: 12.0	weak [IC50 47 uM]
UGT1A1 249	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 10, 55	weak [Inhibition 300 uM]
UGT1A6 139	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 10, 55	weak [Inhibition 300 uM]
UGT1A9 120	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 10, 55	weak [Inhibition 300 uM]
UGT2B7 156	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 10, 55, 64	weak [Inhibition 300 uM]
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_ClinPharmR_P1.pdf Page: 23.0	weak
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_ClinPharmR_P1.pdf Page: 23.0	weak
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_ClinPharmR_P1.pdf Page: 23.0	weak

Drug as victim

Target	Modality	Activity
BSEP 52	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 61.0	likely
MRP2 196	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 61.0	likely
CYP2C19 955	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 9.0	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 9.0	yes
CYP3A5 383	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 9.0	yes
OATP1B1 389	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022081s041lbl.pdf Page: 12.0	yes
P-gp 1491	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 61.0	yes
UGT1A3 421	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 9.0	yes
UGT1A9 378	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 9.0	yes
UGT2B7 387	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022081s000_PharmR_P1.pdf Page: 9.0	yes

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA0024ZZ	http://www.aablocks.com/goods/Goods/detail?id=AA0024ZZ
AEchem Scientific Corp., USA	AE024026	http://www.aechemsc.com/info_products/AE024026.php
AK Scientific, Inc. (AKSCI)	66500	http://www.aksci.com/item_detail.php?cat=66500
Aaron Chemicals	AR0025RR	http://www.aaronchem.com/177036-94-1
Achemtek	0102-012312	http://www.achemtek.com/177036-94-1
Acorn PharmaTech	ACN-030051	http://www.acornpharmatech.com/
Adooq BioScience	A11291	https://www.adooq.com/ambrisentan.html
Alsachim	1485	http://www.alsachim.com/product-C2081-glo.bal-view.html
Anward	ANW-59416	http://www.anward.com/pro_result/45867
ApexBio Technology	B2075	http://www.apexbt.com/ambrisentan-26523.html
AstaTech, Inc.	FD7219	http://www.astatechinc.com/CPSResult.php?CRNO=37302
Aurora Fine Chemicals LLC	A24.076.624	http://online.aurorafinechemicals.com/info?ID=A24.076.624
Aurum Pharmatech LLC	K-5435	http://www.Aurumpharmatech.com/Product/ProductDetails/K_5435
AvaChem Scientific	2664	http://www.avachem.com/productSearch.asp?2664
Axon MedChem	1648	https://www.axonmedchem.com/product/1648
BLD Pharm	BD118907	http://www.bldpharm.com/products/177036-94-1.html
BioSynth	J-519579	https://www.biosynth.com/en/products/all-products/products/J-519579.html
Boerchem	BC224510	http://www.boerchem.com/?product_37829.html
CSNpharm	CSN10496	https://www.csnpharm.com/products/ambrisentan.html
Capot Chemical	18318	http://www.capotchem.com/en/18318.htm
Capot Chemical	PubChem18318	http://www.capotchem.com/en/18318.htm
Chem Scene	CS-0447	http://www.chemscene.com/177036-94-1.html
ChemMol	30114223	http://www.chemmol.com/chemmol/30114223.html
ChemMol	44007214	http://www.chemmol.com/chemmol/44007214.html
Chemspace	CSSB00015191759	https://chem-space.com/CSSB00015191759
Clearsynth	CS-O-00462	https://www.clearsynth.com/en/CSO00462.html
Excenen	EX-A3315	https://www.excenen.com/searchresultlist.php?id=177036-94-1
Hairui	HR136588	http://www.hairuichem.com/en/product/177036-94-1.html
LGC Standards	MM3756.00-0250	https://www.lgcstandards.com/US/en/p/MM3756.00-0250
Lab Network	LN00130941	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00130941
Matrix Scientific	149338	https://www.matrixscientific.com/149338.html
MedChem Express	HY-13209	https://www.medchemexpress.com/Ambrisentan.html
Oakwood	221767	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=102766&ExtHyperLink=1
Smolecule	S518340	http://www.smolecule.com/products/s518340
Synblock Inc	SB17358	http://www.synblock.com/product/177036-94-1.html
TCI (Tokyo Chemical Industry)	A2966	http://www.tcichemicals.com/eshop/en/us/commodity/A2966/index.html
THE BioTek	bt-258891	https://www.thebiotek.com/product/inhibitors/bt-258891
Tocris	5828	https://www.tocris.com/products/ambrisentan_5828
TripleBond	CA0131	http://www.triplebond-canada.com/prod/1093/
VladaChem	VL279151-25MG	https://www.vladachem.com/product.php?products=177036-94-1
Yuhao Chemical	JZ1234	http://www.chemyuhao.com/177036-94-1.html
abcr GmbH	AB436215	http://www.abcr.com/shop/en/AB436215
eNovation Chemicals	K09791	https://www.enovationchem.com/ProductDetails.asp?ProductID=K09791
iChemical	EBD31205	http://www.ichemical.com/products/177036-94-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Endothelin A-receptor blockade in experimental diabetes improves glucose balance and gastrointestinal function.	2002 Aug	12193138
Effect of the novel endothelin(A) receptor antagonist LU 208075 on contraction and relaxation of isolated rat basilar artery.	2002 Aug	12193134
Cerebrovascular characterization of the novel nonpeptide endothelin-A receptor antagonist LU 208075.	2003 Mar-Apr	12671526
Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists.	2004 May 20	15139756
Changes of vasoregulatory gene expression following hepatic ischemia/reperfusion and treatment with endothelin-A receptor blockade.	2004 Nov	15838252
Gateways to clinical trials.	2004 Oct	15605126
Drug Insight: endothelin-receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases.	2005 Dec	16932638
Improvement of postischemic hepatic microcirculation after endothelinA receptor blockade--endothelin antagonism influences platelet-endothelium interactions.	2005 Feb	15694814
Ambrisentan for pulmonary arterial hypertension.	2005 Jul	19804142
Attenuation of proinflammatory gene expression and microcirculatory disturbances by endothelin A receptor blockade after orthotopic liver transplantation in pigs.	2006 Jan	16364719
Endothelin antagonism prevents diabetic retinopathy in NOD mice: a potential role of the angiogenic factor adrenomedullin.	2006 Jun	16741057
Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug.	2006 Jun	16740981
Endothelin receptor antagonists.	2006 Jun	16219361
[Pulmonary hypertension and right ventricular failure. Part XI. Endothelin receptor blockers in the treatment of primary pulmonary arterial hypertension].	2007	18260899
Gateways to clinical trials.	2007 Apr	17520107
Ambrisentan (Letairis) for pulmonary arterial hypertension.	2007 Oct 22	17938611
Ambrisentan.	2008	18840007
Endothelin receptor antagonism: role in the treatment of pulmonary arterial hypertension related to scleroderma.	2008	18681488
[Treatment of pulmonary arterial hypertension by endothelin receptor antagonists in 2008].	2008 Apr	18243424
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	19924277
Pulmonary hypertension: past, present and future.	2008 Jan	19561874
The management of pulmonary hypertension in children.	2008 Jul	18381346
Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.	2008 Jun 10	18506008
Gateways to clinical trials.	2008 Mar	18560631
[Systemic sclerosis].	2008 May	18552072
Role of ambrisentan in the management of pulmonary hypertension.	2008 Nov	18957622
Therapeutic methods used in patients with Eisenmenger syndrome.	2009	19950085
Use of inhaled iloprost in an infant with bronchopulmonary dysplasia and pulmonary artery hypertension.	2009 Aug	19949642
[Endothelin receptor antagonists - their role in pulmonary medicine].	2009 Dec	20032843
Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease.	2009 Dec	19775299
No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers.	2009 Dec	19455620
Ambrisentan for the treatment of pulmonary arterial hypertension.	2009 Feb 6	19920913
Small-molecule endothelin receptor antagonists: a review of patenting activity across therapeutic areas.	2009 Jun	19517317
Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis.	2009 Jun	19487219
Gateways to clinical trials.	2009 Nov	20094643
Gateways to clinical trials.	2009 Sep	19907722
Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis.	2010 Jan 29	20113497

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

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 [INN]

Common Name

English

AMBRISENTAN [EMA EPAR]

Common Name

English

Ambrisentan [WHO-DD]

Common Name

English

GSK-1325760A

Code

English

AMBRISENTAN [VANDF]

Common Name

English

AMBRISENTAN, (+)-

Common Name

English

Classification Tree Code System Code

WHO-ATC

C02KX52