Ambrisentan

Identification

Summary

Ambrisentan is a selective type A endothelin receptor antagonist used to treat primary pulmonary arterial hypertension and pulmonary arterial hypertension based on diagnostic classifications.

Brand Names
Letairis
Generic Name
Ambrisentan
DrugBank Accession Number
DB06403
Background

Ambrisentan is an orally active selective type A endothelin receptor antagonist 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. Studies establishing the efficacy of Ambrisentan included patients with both idiopathic or heritable pulmonary arterial hypertension and those with pulmonary arterial hypertension associated with connective tissue diseases. Patients studied displayed symptoms and etiologies predominantly of WHO Functional Class II-III. 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 378.428
Monoisotopic: 378.157957196
Chemical Formula
C22H22N2O4
Synonyms
  • (2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy- 3,3-diphenylpropanoic acid
  • Ambrisentan
External IDs
  • BSF 208075
  • BSF-208075
  • BSF208075
  • GSK-1325760
  • GSK-1325760A
  • GSK1325760
  • GSK1325760A
  • LU 208075
  • LU-208075
  • LU208075

Pharmacology

Indication

Ambrisentan is indicated for treatment of idiopathic (‘primary’) pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension (PAH) associated with connective tissue disease in patients with WHO functional class II or III symptoms. In the United States of America, ambrisentan is also indicated in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofWho group 1 pulmonary arterial hypertension••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Ambrisentan 10 mg daily had no significant effect on the QTc interval, whereas a 40 mg daily dose of ambrisentan increased mean QTc at tmax by 5 ms with an upper 95% confidence limit of 9 ms. Significant QTc prolongation is not expected in patients taking ambrisentan without concomitant metabolic inhibitors. Plasma concentrations of B-type natriuretic peptide (BNP) in patients who received ambrisentan for 12 weeks were significantly decreased. Two Phase III placebo-controlled studies demonstrated a decrease in BNP plasma concentrations by 29% in the 2.5 mg group, 30% in the 5 mg group, and 45% in the 10 mg group (p < 0.001 for each dose group) and an increase by 11% in the placebo group.

Mechanism of action

Endothelin-1 (ET-1) is an endogenous peptide that acts on the endothelin type A (ETA) and endothelin type B (ETB) receptors in vascular smooth muscle and endothelium. ETA-mediated actions include vasoconstriction and cell proliferation, whereas ETB predominantly mediates vasodilation, anti-proliferation, and ET-1 clearance. In patients with pulmonary arterial hypertension, ET-1 levels are increased and correlate with increased right arterial pressure and severity of disease. Ambrisentan is one of several newly developed vasodilator drugs that selectively target the endothelin type A (ETA) receptor, inhibiting its action and preventing vasoconstriction. Selective inhibition of the ETA receptor prevents phospholipase C-mediated vasoconstriction and protein kinase C-mediated cell proliferation. Endothelin type B (ETB) receptor function is not significantly inhibited, and nitric oxide and prostacyclin production, cyclic GMP- and cyclic AMP-mediated vasodilation, and endothelin-1 (ET-1) clearance is preserved.

TargetActionsOrganism
AEndothelin-1 receptor
antagonist
Humans
NEndothelin B receptor
antagonist
Humans
Absorption

Ambrisentan is rapidly absorbed with peak plasma concentrations occuring around 2 hours after oral administration. Cmax and AUC increase proportionally with dose across the therapeutic dosing range. Absolute oral bioavailability of ambrisentan is unknown. Absorption is not affected by food.

Volume of distribution

Ambrisentan has a low distribution into red blow cells, with a mean blood:plasma ratio of 0.57 and 0.61 in males and females, respectively.

Protein binding

Ambrisentan is 99% plasma protein bound, primarily to albumin (96.5%) and to a lesser degree alpha1-acid glycoprotein.

Metabolism

Ambrisentan is a metabolized primarily by uridine 5’-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S,1A3S to form ambrisentan glucuronide. Ambrisentan is also metabolized to a lesser extent by CYP3A4, CYP3A5 and CYP2C19 to form 4- hydroxymethyl ambrisentan which is further glucuronidated to 4-hydroxymethyl ambrisentan glucuronide.

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Route of elimination

Ambrisentan is primarily cleared by non-renal pathways. Along with its metabolites, ambrisentan is primarily found in the feces following hepatic and/or extra-hepatic metabolism. Approximately 22% of the administered dose is recovered in the urine following oral administration with 3.3% being unchanged ambrisentan.

Half-life

Ambrisentan has a terminal half-life of 15 hours. It is thought that steady state is achieved after around 4 days of repeat-dosing.

Clearance

The mean oral clearance of ambrisentan was found to be 38 mL/min in healthy subjects and 19 mL/min in patients with pulmonary artery hypertension.

Adverse Effects
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Toxicity

Ambrisentan is teratogenic and has a high risk of embryo-fetal toxicity. LD50 was found to be greater than or equal to 3160 mg/kg when studied in rats. There was no evidence of carcinogenic potential in 2 year oral daily dosing studies in rats and mice.

Pathways
Not Available
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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideAbaloparatide may increase the hypotensive activities of Ambrisentan.
AbametapirThe serum concentration of Ambrisentan can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Ambrisentan can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Ambrisentan.
AbrocitinibThe serum concentration of Ambrisentan can be increased when it is combined with Abrocitinib.
Food Interactions
No interactions found.

Products

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International/Other Brands
Ambrican (Lupin) / Endobloc (Cipla Ltd.) / Pulmonext (MSN Labs) / Zambri (German Remedies Ltd.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ambrisentan MylanTablet, film coated5 mgOralMylan S.A.S.2020-12-16Not applicableEU flag
Ambrisentan MylanTablet, film coated10 mgOralMylan S.A.S.2020-12-16Not applicableEU flag
Ambrisentan MylanTablet, film coated10 mgOralMylan S.A.S.2020-12-16Not applicableEU flag
Ambrisentan MylanTablet, film coated5 mgOralMylan S.A.S.2020-12-16Not applicableEU flag
Ambrisentan MylanTablet, film coated5 mgOralMylan S.A.S.2020-12-16Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmbrisentanTablet, film coated10 mg/1OralSun Pharmaceutical Industries, Inc.2019-04-29Not applicableUS flag
AmbrisentanTablet, film coated10 mg/1OralExelan Pharmaceuticals, Inc.2020-07-22Not applicableUS flag
AmbrisentanTablet, film coated5 mg/1OralMylan Pharmaceuticals Inc.2019-04-29Not applicableUS flag
AmbrisentanTablet, film coated5 mg/1OralCipla USA Inc.2019-04-26Not applicableUS flag
AmbrisentanTablet, film coated10 mg/1OralZydus Pharmaceuticals USA Inc.2019-04-12Not applicableUS flag

Categories

ATC Codes
C02KX02 — AmbrisentanC02KX52 — Ambrisentan and tadalafil
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Phenylpropanoic acids / Benzylethers / Alkyl aryl ethers / Pyrimidines and pyrimidine derivatives / Monosaccharides / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Dialkyl ethers / Carboxylic acids / Azacyclic compounds
show 5 more
Substituents
3-phenylpropanoic-acid / Alkyl aryl ether / Aromatic heteromonocyclic compound / Azacycle / Benzylether / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Dialkyl ether / Diphenylmethane
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
HW6NV07QEC
CAS number
177036-94-1
InChI Key
OUJTZYPIHDYQMC-LJQANCHMSA-N
InChI
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
IUPAC Name
(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid
SMILES
COC([C@H](OC1=NC(C)=CC(C)=N1)C(O)=O)(C1=CC=CC=C1)C1=CC=CC=C1

References

Synthesis Reference
  • Riechers H, Albrecht HP, Amberg W, Baumann E, Bernard H, Bohm HJ, Klinge D, Kling A, Muller S, Raschack M, Unger L, Walker N, Wernet W: Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists. J Med Chem. 1996 May 24;39(11):2123-8. Pubmed.
  • Peng X, Li P, Shi Y: Synthesis of (+)-ambrisentan via chiral ketone-catalyzed asymmetric epoxidation. J Org Chem. 2012 Jan 6;77(1):701-3. doi: 10.1021/jo201927m. Epub 2011 Nov 29. Pubmed.
General References
  1. Said K: AMBITION: An important piece in the therapeutic puzzle of pulmonary arterial hypertension. Glob Cardiol Sci Pract. 2015 Nov 13;2015(4):48. doi: 10.5339/gcsp.2015.48. eCollection 2015. [Article]
  2. Markert C, Wirsching T, Hellwig R, Burhenne J, Weiss J, Riedel KD, Mikus G, Haefeli WE: Lack of a clinically significant interaction of grapefruit juice with ambrisentan and bosentan in healthy adults. Int J Clin Pharmacol Ther. 2014 Nov;52(11):957-64. doi: 10.5414/CP202164. [Article]
  3. Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ: 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. Circulation. 2008 Jun 10;117(23):3010-9. doi: 10.1161/CIRCULATIONAHA.107.742510. Epub 2008 May 27. [Article]
  4. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
  5. Peacock AJ, Zamboni W, Vizza CD: Ambrisentan for the treatment of adults with pulmonary arterial hypertension: a review. Curr Med Res Opin. 2015;31(9):1793-807. doi: 10.1185/03007995.2015.1074890. Epub 2015 Aug 27. [Article]
  6. Casserly B, Klinger JR: Ambrisentan for the treatment of pulmonary arterial hypertension. Drug Des Devel Ther. 2009 Feb 6;2:265-80. [Article]
  7. Kingman M, Ruggiero R, Torres F: Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2009 Aug;10(11):1847-58. doi: 10.1517/14656560903061275. [Article]
  8. Buckley MS, Wicks LM, Staib RL, Kirejczyk AK, Varker AS, Gibson JJ, Feldman JP: Pharmacokinetic evaluation of ambrisentan. Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):371-80. doi: 10.1517/17425255.2011.557181. Epub 2011 Feb 8. [Article]
PubChem Compound
6918493
PubChem Substance
310264868
ChemSpider
5293690
BindingDB
50146710
RxNav
358274
ChEBI
135949
ChEMBL
CHEMBL1111
ZINC
ZINC000000538627
PharmGKB
PA165860521
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ambrisentan
FDA label
Download (1.74 MB)
MSDS
Download (94.4 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
PowderNot applicable1 kg/1kg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral
Tablet, film coatedOral10 mg
Tablet, film coatedOral5 mg
Tablet, coatedOral10 mg
Tablet, film coatedOral500000 mg
TabletOral10 mg
TabletOral5 mg
Tablet, film coatedOral2.5 mg
Tablet, film coatedOral10.0 mg
Tablet, film coatedOral5.0 mg
Tablet, coatedOral5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5703017No1997-12-302014-12-30US flag
CA2201785No2006-08-292015-10-07Canada flag
US5840722No1998-11-242015-11-24US flag
US7601730No2009-10-132015-10-07US flag
US8377933No2013-02-192027-12-11US flag
US7109205No2006-09-192015-10-07US flag
USRE42462No2011-06-142018-07-29US flag
US8349843No2013-01-082015-10-07US flag
US9474752No2016-10-252027-12-11US flag
US9549926No2017-01-242031-10-14US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)165-168 °C# Riechers H, Albrecht HP, Amberg W, Baumann E, Bernard H, Bohm HJ, Klinge D, Kling A, Muller S, Raschack M, Unger L, Walker N, Wernet W: Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists. J Med Chem. 1996 May 24;39(11):2123-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/8667356
water solubilityAmbrisentan is practically insoluble in aqueous solutions at low pH. Solubility increases at higher pH.# FDA Label
pKa4.0# FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.05 mg/mLALOGPS
logP3.9ALOGPS
logP3.5Chemaxon
logS-3.9ALOGPS
pKa (Strongest Acidic)3.59Chemaxon
pKa (Strongest Basic)2.48Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area81.54 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity104.17 m3·mol-1Chemaxon
Polarizability38.86 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fb9-0519000000-334b60bcbe0d4e18e21c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uka-0029000000-e0b04d1776fcf8170fe9
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0419000000-a792f83199b48d828f08
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-4859000000-156d550506f5879178e6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-5912000000-3fcbeb618534533172c8
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a59-9601000000-95f62db4ceea52732a82
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-05gi-0900000000-955e0a310b2ac60841a2
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-199.9499013
predicted
DarkChem Lite v0.1.0
[M-H]-183.76973
predicted
DeepCCS 1.0 (2019)
[M+H]+200.2980013
predicted
DarkChem Lite v0.1.0
[M+H]+186.1653
predicted
DeepCCS 1.0 (2019)
[M+Na]+200.4034013
predicted
DarkChem Lite v0.1.0
[M+Na]+192.07782
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
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Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is:...
Gene Name
EDNRA
Uniprot ID
P25101
Uniprot Name
Endothelin-1 receptor
Molecular Weight
48721.76 Da
References
  1. Spence R, Mandagere A, Richards DB, Magee MH, Dufton C, Boinpally R: Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin Pharmacol Ther. 2010 Oct;88(4):513-20. doi: 10.1038/clpt.2010.120. Epub 2010 Sep 1. [Article]
  2. Richards DB, Walker GA, Mandagere A, Magee MH, Henderson LS: Effect of ketoconazole on the pharmacokinetic profile of ambrisentan. J Clin Pharmacol. 2009 Jun;49(6):719-24. doi: 10.1177/0091270009335870. Epub 2009 Apr 23. [Article]
  3. Kingman M, Ruggiero R, Torres F: Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2009 Aug;10(11):1847-58. doi: 10.1517/14656560903061275. [Article]
  4. Casserly B, Klinger JR: Ambrisentan for the treatment of pulmonary arterial hypertension. Drug Des Devel Ther. 2009 Feb 6;2:265-80. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
General Function
Peptide hormone binding
Specific Function
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name
EDNRB
Uniprot ID
P24530
Uniprot Name
Endothelin B receptor
Molecular Weight
49643.255 Da
References
  1. Casserly B, Klinger JR: Ambrisentan for the treatment of pulmonary arterial hypertension. Drug Des Devel Ther. 2009 Feb 6;2:265-80. [Article]
  2. Kingman M, Ruggiero R, Torres F: Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2009 Aug;10(11):1847-58. doi: 10.1517/14656560903061275. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Spence R, Mandagere A, Richards DB, Magee MH, Dufton C, Boinpally R: Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin Pharmacol Ther. 2010 Oct;88(4):513-20. doi: 10.1038/clpt.2010.120. Epub 2010 Sep 1. [Article]
  2. Richards DB, Walker GA, Mandagere A, Magee MH, Henderson LS: Effect of ketoconazole on the pharmacokinetic profile of ambrisentan. J Clin Pharmacol. 2009 Jun;49(6):719-24. doi: 10.1177/0091270009335870. Epub 2009 Apr 23. [Article]
  3. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Buckley MS, Wicks LM, Staib RL, Kirejczyk AK, Varker AS, Gibson JJ, Feldman JP: Pharmacokinetic evaluation of ambrisentan. Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):371-80. doi: 10.1517/17425255.2011.557181. Epub 2011 Feb 8. [Article]
  2. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Buckley MS, Wicks LM, Staib RL, Kirejczyk AK, Varker AS, Gibson JJ, Feldman JP: Pharmacokinetic evaluation of ambrisentan. Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):371-80. doi: 10.1517/17425255.2011.557181. Epub 2011 Feb 8. [Article]
  2. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Buckley MS, Wicks LM, Staib RL, Kirejczyk AK, Varker AS, Gibson JJ, Feldman JP: Pharmacokinetic evaluation of ambrisentan. Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):371-80. doi: 10.1517/17425255.2011.557181. Epub 2011 Feb 8. [Article]
  2. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Buckley MS, Wicks LM, Staib RL, Kirejczyk AK, Varker AS, Gibson JJ, Feldman JP: Pharmacokinetic evaluation of ambrisentan. Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):371-80. doi: 10.1517/17425255.2011.557181. Epub 2011 Feb 8. [Article]
  2. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Venitz J, Zack J, Gillies H, Allard M, Regnault J, Dufton C: Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805. doi: 10.1177/0091270011423662. Epub 2011 Dec 28. [Article]

Drug created at March 19, 2008 16:29 / Updated at February 20, 2024 23:55