bosentan indications/contra

Stem definitionDrug idCAS RN
endothelin receptor antagonists 392 147536-97-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • bosentan hydrate
  • bosentan monohydrate
  • stayveer
  • bosentan
  • actelion
  • tracleer
  • bosentan anhydrous
a specific and competitive antagonist at endothelin receptor types ETA and ETB, has a slightly higher affinity for ETA receptors than for ETB receptors, indicated for the treatment of pulmonary arterial hypertension
  • Molecular weight: 551.62
  • Formula: C27H29N5O6S
  • CLOGP: 4.17
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 2
  • TPSA: 145.65
  • ALOGS: -4.79
  • ROTB: 10

Drug dosage:

DoseUnitRoute
0.25 g O

Approvals:

DateAgencyCompanyOrphan
Nov. 20, 2001 FDA ACTELION PHARMS LTD

FDA Adverse Event Reporting System

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MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 17046.82 40.18 6219 19446 146105 3214089
Dyspnoea 7376.34 40.18 3100 22565 99834 3260360
Pulmonary arterial hypertension 5836.95 40.18 1267 24398 2973 3357221
Aspartate aminotransferase increased 3095.72 40.18 1083 24582 20030 3340164
Pneumonia 3030.99 40.18 1500 24165 68643 3291551
Alanine aminotransferase increased 2856.68 40.18 1051 24614 22589 3337605
Right ventricular failure 2798.84 40.18 643 25022 2100 3358094
Fluid retention 2658.44 40.18 770 24895 7388 3352806
Pulmonary hypertension 2464.87 40.18 691 24974 5819 3354375
Liver function test abnormal 2215.20 40.18 746 24919 12155 3348039
Condition aggravated 2169.50 40.18 997 24668 38236 3321958
Blood alkaline phosphatase increased 1885.07 40.18 629 25036 9924 3350270
Fall 1663.63 40.18 952 24713 57931 3302263
Oedema peripheral 1646.66 40.18 792 24873 33569 3326625
Transfusion 1569.26 40.18 398 25267 2154 3358040
Syncope 1510.13 40.18 682 24983 24951 3335243
Respiratory failure 1433.97 40.18 638 25027 22503 3337691
Cardiac failure congestive 1423.65 40.18 686 24979 29136 3331058
Cardiac failure 1403.75 40.18 603 25062 19502 3340692
Disease progression 1334.08 40.18 673 24992 31586 3328608
Oedema 1262.21 40.18 511 25154 14169 3346025
Pulmonary oedema 1228.47 40.18 473 25192 11438 3348756
Blood bilirubin increased 1154.26 40.18 437 25228 10072 3350122
Chronic obstructive pulmonary disease 1095.31 40.18 426 25239 10583 3349611
Oxygen saturation decreased 1048.36 40.18 403 25262 9688 3350506
Dizziness 1038.75 40.18 783 24882 75729 3284465
Cough 1023.38 40.18 607 25058 39251 3320943
Fluid overload 1018.27 40.18 308 25357 3443 3356751
Chest pain 983.69 40.18 594 25071 39681 3320513
Lung transplant 965.94 40.18 212 25453 519 3359675

Pharmacologic Action:

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SourceCodeDescription
ATC C02KX01 CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
OTHER ANTIHYPERTENSIVES
Antihypertensives for pulmonary arterial hypertension
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D065128 Endothelin Receptor Antagonists
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:51451 endothelin receptor antagonist

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Pulmonary arterial hypertension indication 11399002
Pulmonary hypertension indication 70995007 DOID:6432
Systemic sclerosis indication 89155008 DOID:419
Hyperbilirubinemia contraindication 14783006 DOID:2741
Pulmonary edema contraindication 19242006 DOID:11396
Hepatic failure contraindication 59927004
Pulmonary veno-occlusive disease contraindication 89420002 DOID:5453
Liver function tests abnormal contraindication 166603001
Decompensated cardiac failure contraindication 195111005
Disease of liver contraindication 235856003 DOID:409
Drug-induced hepatitis contraindication 235876009
Edema contraindication 267038008
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.84 acidic
pKa2 2.87 Basic
pKa3 1.44 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
125MG TRACLEER ACTELION PHARMS LTD N021290 Nov. 20, 2001 RX TABLET ORAL Sept. 5, 2020 NEW PATIENT POPULATION
62.5MG TRACLEER ACTELION PHARMS LTD N021290 Nov. 20, 2001 RX TABLET ORAL Sept. 5, 2020 NEW PATIENT POPULATION
32MG TRACLEER ACTELION PHARMS N209279 Sept. 5, 2017 RX TABLET, FOR SUSPENSION ORAL Sept. 5, 2020 NEW PRODUCT
32MG TRACLEER ACTELION PHARMS N209279 Sept. 5, 2017 RX TABLET, FOR SUSPENSION ORAL Sept. 5, 2024 TREATMENT OF PULMONARY ARTERIAL HYPERTENSION (PAH) (WHO GROUP 1) IN PEDIATRIC PATIENTS AGED 3 YRS AND OLDER WITH IDIOPATHIC OR CONGENITAL PAH TO IMPROVE PULMONARY VASCULAR RESISTANCE (PVR), WHICH IS EXPECTED TO RESULT IN AN IMPROVEMENT IN EXERCISE ABILITY

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Endothelin B receptor GPCR ANTAGONIST Ki 7.10 CHEMBL CHEMBL
Endothelin-1 receptor GPCR ANTAGONIST Ki 8.19 CHEMBL CHEMBL
Bile salt export pump Transporter IC50 4.42 CHEMBL
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor WOMBAT-PK
Endothelin-1 receptor GPCR IC50 8.12 CHEMBL
Bile salt export pump Unclassified IC50 4.51 CHEMBL
Endothelin B receptor Unclassified IC50 7.02 CHEMBL
Endothelin-1 receptor GPCR Ki 8.19 CHEMBL

External reference:

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IDSource
DB00559 DRUGBANK_ID
3494 IUPHAR_LIGAND_ID
C1529800 UMLSCUI
D01227 KEGG_DRUG
CHEMBL957 ChEMBL_ID
N0000010080 NDFRT
N0000148726 NDFRT
009514 NDDF
d04782 MMSL
16217 MMSL
75207 RXNORM
4021289 VANDF
385558007 SNOMEDCT_US
385559004 SNOMEDCT_US
104865 PUBCHEM_CID
Q326023R30 UNII
157212-55-0 SECONDARY_CAS_RN
7195 INN_ID
C086232 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:51450 CHEBI
K86 PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Tracleer HUMAN PRESCRIPTION DRUG LABEL 1 66215-101 TABLET, FILM COATED 62.50 mg ORAL NDA 20 sections
Tracleer HUMAN PRESCRIPTION DRUG LABEL 1 66215-102 TABLET, FILM COATED 125 mg ORAL NDA 20 sections
Tracleer HUMAN PRESCRIPTION DRUG LABEL 1 66215-103 TABLET, SOLUBLE 32 mg ORAL NDA 20 sections