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Bosentan

PubChem CID
104865
Structure
Bosentan_small.png
Bosentan_3D_Structure.png
Molecular Formula
Synonyms
  • Bosentan
  • 147536-97-8
  • Tracleer
  • bosentan anhydrous
  • Actelion
Molecular Weight
551.6 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-11
Description
Bosentan is a sulfonamide, a member of pyrimidines and a primary alcohol. It has a role as an antihypertensive agent and an endothelin receptor antagonist.
Bosentan is a dual endothelin receptor antagonist marketed under the trade name Tracleer by Actelion Pharmaceuticals. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.
Bosentan anhydrous is an Endothelin Receptor Antagonist. The mechanism of action of bosentan anhydrous is as an Endothelin Receptor Antagonist, and Cytochrome P450 3A Inducer, and Cytochrome P450 2C9 Inducer.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Bosentan.png

1.2 3D Conformer

1.3 Crystal Structures

COD records with this CID as component

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

GJPICJJJRGTNOD-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC2=C(C(=NC(=N2)C3=NC=CC=N3)OCCO)OC4=CC=CC=C4OC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C27H29N5O6S
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

157212-55-0

2.3.2 Deprecated CAS

174227-18-0

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 PharmGKB ID

2.3.15 Pharos Ligand ID

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 4-t-butyl-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide
  • bosentan
  • bosentan anhydrous
  • bosentan monohydrate
  • Ro 47 0203
  • Ro 47-0203
  • Ro 470203
  • Ro-47-0203
  • Tracleer

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
551.6 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
3.8
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
11
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
11
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
551.18385484 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
551.18385484 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
154 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
39
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
839
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Solubility

Poorly soluble in water (1.0 mg/100 ml) and in aqueous solutions at low pH (0.1 mg/100 ml at pH 1.1 and 4.0; 0.2 mg/100 ml at pH 5.0). Solubility increases at higher pH values (43 mg/100 ml at pH 7.5).
9.04e-03 g/L

3.2.3 LogP

3.7
3.7

3.2.4 Caco2 Permeability

-5.98
ADME Research, USCD

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceuticals -> Antihypertensives
S57 | GREEKPHARMA | Suspect Pharmaceuticals from the National Organization of Medicine, Greece | DOI:10.5281/zenodo.3248883
Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents
Human drug -> Prescription
Human drug -> Prescription; None (Tentative Approval); Discontinued; Active ingredient (BOSENTAN)
Human drugs -> Antihypertensives -> Human pharmacotherapeutic group -> EMA Drug Category
Human drugs -> Other antihypertensives -> Human pharmacotherapeutic group -> EMA Drug Category
Paediatric drug

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 MS-MS

1 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

202.0717 100

280.0828 49.50

203.0762 15.28

281.0855 8.68

149.0447 8.12

Thumbnail
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2 of 6
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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

552.1911 100

553.1943 29.21

508.1642 3.17

202.071 1.43

311.1005 1.26

Thumbnail
Thumbnail

4.1.2 LC-MS

1 of 43
View All
Authors
Nikiforos Alygizakis, Katerina Galani, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
9.959 min
Precursor m/z
552.1911
Precursor Adduct
[M+H]+
Top 5 Peaks

552.1911 999

553.1941 295

554.1925 71

Thumbnail
Thumbnail
License
CC BY
2 of 43
View All
Authors
Nikiforos Alygizakis, Katerina Galani, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
9.991 min
Precursor m/z
552.1911
Precursor Adduct
[M+H]+
Top 5 Peaks

552.1911 999

553.1943 291

508.1642 31

202.071 14

311.1005 12

Thumbnail
Thumbnail
License
CC BY

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Used in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).
Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III. Efficacy has been shown in: , , , Primary (idiopathic and familial) PAH; , PAH secondary to scleroderma without significant interstitial pulmonary disease; , PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger's physiology. , , , Some improvements have also been shown in patients with PAH WHO functional class II. , , Tracleer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease. ,

7.2 LiverTox Summary

Bosentan is an endothelin receptor antagonist used in the therapy of pulmonary arterial hypertension (PAH). Bosentan has been associated with serum enzyme elevations during therapy and with rare instances of clinically apparent acute liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents
Pulmonary Arterial Hypertension Agents

7.4 FDA Medication Guides

Drug
Active Ingredient
BOSENTAN
Form;Route
TABLET;ORAL
Company
ACTELION
Date
02/08/2024
Drug
Active Ingredient
BOSENTAN
Form;Route
TABLET, FOR SUSPENSION;ORAL
Company
ACTELION
Date
02/08/2024

7.5 FDA Approved Drugs

7.6 FDA Orange Book

7.7 FDA National Drug Code Directory

7.8 Drug Labels

Drug and label
Active ingredient and drug

7.9 Clinical Trials

7.9.1 ClinicalTrials.gov

7.9.2 EU Clinical Trials Register

7.9.3 NIPH Clinical Trials Search of Japan

7.10 EMA Drug Information

1 of 3
View All
Medicine
Category
Human drugs
Therapeutic area
Scleroderma, Systemic; Hypertension, Pulmonary
Active Substance
bosentan (as monohydrate)
INN/Common name
bosentan
Pharmacotherapeutic Classes
Antihypertensives
Status
This medicine is authorized for use in the European Union
Company
Janssen-Cilag International N.V.  
Market Date
2002-05-14
2 of 3
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Medicine
Category
Human drugs
Therapeutic area
Hypertension, Pulmonary; Scleroderma, Systemic
Active Substance
bosentan (as monohydrate)
INN/Common name
bosentan monohydrate
Pharmacotherapeutic Classes
Other antihypertensives
Status
This medicine is authorized for use in the European Union
Company
Janssen-Cilag International NV
Market Date
2013-06-24

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Bosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.

8.2 MeSH Pharmacological Classification

Antihypertensive Agents
Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)
Endothelin Receptor Antagonists
Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN RECECPTORS. (See all compounds classified as Endothelin Receptor Antagonists.)

8.3 FDA Pharmacological Classification

1 of 2
FDA UNII
XUL93R30K2
Active Moiety
BOSENTAN ANHYDROUS
Pharmacological Classes
Established Pharmacologic Class [EPC] - Endothelin Receptor Antagonist
Pharmacological Classes
Mechanisms of Action [MoA] - Endothelin Receptor Antagonists
Pharmacological Classes
Mechanisms of Action [MoA] - Cytochrome P450 3A Inducers
Pharmacological Classes
Mechanisms of Action [MoA] - Cytochrome P450 2C9 Inducers
FDA Pharmacology Summary
Bosentan anhydrous is an Endothelin Receptor Antagonist. The mechanism of action of bosentan anhydrous is as an Endothelin Receptor Antagonist, and Cytochrome P450 3A Inducer, and Cytochrome P450 2C9 Inducer.
2 of 2
Non-Proprietary Name
BOSENTAN
Pharmacological Classes
Cytochrome P450 3A Inducers [MoA]; Cytochrome P450 2C9 Inducers [MoA]; Endothelin Receptor Antagonist [EPC]; Endothelin Receptor Antagonists [MoA]

8.4 ATC Code

C02KX01
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

C - Cardiovascular system

C02 - Antihypertensives

C02K - Other antihypertensives

C02KX - Antihypertensives for pulmonary arterial hypertension

C02KX01 - Bosentan

8.5 Absorption, Distribution and Excretion

Absorption
Absolute bioavailability is approximately 50% and food does not affect absorption.
Route of Elimination
Bosentan is eliminated by biliary excretion following metabolism in the liver.
Volume of Distribution
18 L
Clearance
4 L/h [patients with pulmonary arterial hypertension]

8.6 Metabolism / Metabolites

Bosentan is metabolized in the liver by the cytochrome P450 enzymes CYP2C9 and CYP3A4 (and possibly CYP2C19), producing three metabolites, one of which, Ro 48-5033, is pharmacologically active and may contribute 10 to 20% to the total activity of the parent compound.
Bosentan has known human metabolites that include 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-hydroxyphenoxy)-[2,2-]bipyrimidinyl-4-yl]-benzenesulfonamide and Hydroxy Bosentan.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

8.7 Biological Half-Life

Terminal elimination half-life is about 5 hours in healthy adult subjects.

8.8 Mechanism of Action

Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ETA and ETB receptors in the endothelium and vascular smooth muscle. It displays a slightly higher affinity towards ETA receptors than ETB receptors. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET-1 in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ETA and ETB.

8.9 Human Metabolite Information

8.9.1 Cellular Locations

Membrane

8.10 Transformations

9 Use and Manufacturing

9.1 Uses

Use (kg; approx.) in Germany (2009): >100

Consumption (g per capita; approx.) in Germany (2009): 0.00122

Calculated removal (%): 15.4

9.1.1 Use Classification

Human drugs -> Antihypertensives -> Human pharmacotherapeutic group -> EMA Drug Category
Human drugs -> Other antihypertensives -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

1 of 3
View All
Pictogram(s)
Irritant
Health Hazard
Signal
Warning
GHS Hazard Statements

H302 (27.3%): Harmful if swallowed [Warning Acute toxicity, oral]

H312 (18.2%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H315 (27.3%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (18.2%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (27.3%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H332 (27.3%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H335 (18.2%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H361 (63.6%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H412 (27.3%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P203, P261, P264, P264+P265, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 11 reports by companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

10.1.2 Hazard Classes and Categories

Acute Tox. 4 (27.3%)

Acute Tox. 4 (18.2%)

Skin Irrit. 2 (27.3%)

Skin Sens. 1 (18.2%)

Eye Irrit. 2 (27.3%)

Acute Tox. 4 (27.3%)

STOT SE 3 (18.2%)

Repr. 2 (63.6%)

Aquatic Chronic 3 (27.3%)

Acute Tox. 4 (50%)

Repr. 1B (25%)

Repr. 2 (75%)

Aquatic Chronic 3 (75%)

11 Toxicity

11.1 Toxicological Information

11.1.1 Hepatotoxicity

Bosentan is associated with elevations in serum aminotransferase levels above three times the upper limit of the normal range (ULN) in 3% to 18% of patients, averaging 7.6% using currently recommended doses. The enzyme elevations are usually self-limited and are rarely accompanied by symptoms, but can be more marked and persist and require dose reduction or discontinuation (in 3% to 4% of patients). Monthly monitoring of serum aminotransferase levels is recommended, with discontinuation for levels above 8 times the ULN or for values above 5 times the ULN that persist. There have also been rare reports of clinically apparent liver injury with jaundice associated with bosentan use. The onset of illness was usually within 1 to 6 months of starting bosentan, but cases arising during chronic therapy have also been described (Case 1). The enzyme pattern has typically been hepatocellular or mixed. Immunoallergic features are usually not present and autoantibodies are usually absent or present in low titer. Some cases have been severe and fatalities have been reported, but there have been no published reports of chronic hepatitis or vanishing bile duct syndrome attributed to bosentan. Autoimmune and immunoallergic features are usually not present.

Likelihood score: C (probable cause of clinically apparent liver injury).

11.1.2 Drug Induced Liver Injury

Compound
bosentan
DILI Annotation
Most-DILI-Concern
Severity Grade
7
Label Section
Box warning
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

11.1.3 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

A study in one patient taking bosentan during breastfeeding found very low levels in milk. Another woman breastfed her preterm newborn while taking bosentan and sildenafil with no adverse effects reported. Amounts ingested by the infant are far below doses given to treat infants and would not be expected to cause any adverse effects in breastfed infants.

◉ Effects in Breastfed Infants

A 23-year-old woman with congenital heart disease and pulmonary hypertension was treated during pregnancy with bosentan and sildenafil in unspecified dosages. These drugs and warfarin were continued postpartum. Her infant was delivered at 30 weeks by cesarean section and weighed 1.41 kg at birth. She nursed the infant in the neonatal intensive care unit for 11 weeks "with good outcome" according to the authors, but the infant died at 26 weeks from a respiratory syncytial virus infection.[2]

A woman breastfeeding her 21-month-old infant was taking 20 mg of sildenafil 3 times daily and 125 mg of bosentan twice daily to treat pulmonary arterial hypertension. The drugs were begun more than 6 months postpartum. The mother did not report any possible adverse effects, serious health problem or hospitalization of the infant in the period from birth until day 651 postpartum when the infant continued to be partially breastfed.[1]

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

11.1.4 Protein Binding

Greater than 98% to plasma proteins, mainly albumin.

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Chemical Co-Occurrences in Literature

13.6 Chemical-Gene Co-Occurrences in Literature

13.7 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 FDA Orange Book Patents

14.4 Chemical Co-Occurrences in Patents

14.5 Chemical-Disease Co-Occurrences in Patents

14.6 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Protein Bound 3D Structures

15.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

15.2 Chemical-Target Interactions

15.3 Drug-Drug Interactions

15.4 Drug-Food Interactions

Take with or without food. The absorption is unaffected by food.

16 Biological Test Results

16.1 BioAssay Results

17 Taxonomy

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: ATC

18.5 KEGG: Target-based Classification of Drugs

18.6 KEGG: Drug Groups

18.7 WHO ATC Classification System

18.8 FDA Pharm Classes

18.9 ChemIDplus

18.10 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

18.11 ChEMBL Target Tree

18.12 UN GHS Classification

18.13 NORMAN Suspect List Exchange Classification

18.14 EPA DSSTox Classification

18.15 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)(2,2'-bipyrimidin)-4-yl)benzenesulfonamide monohydrate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.149.340
    (2S)-3-Methyl-2-[pentanoyl-[[2'-(1H-tetrazol-5-yl)phenyl]phenyl]-4-ylmethyl]amino]butanoic acid
    https://echa.europa.eu/substance-information/-/substanceinfo/100.171.206
    4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide Monohydrate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.219.414
    4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)(2,2'-bipyrimidin)-4-yl)benzenesulfonamide monohydrate (EC: 620-486-3)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/153783
    (2S)-3-Methyl-2-[pentanoyl-[[2'-(1H-tetrazol-5-yl)phenyl]phenyl]-4-ylmethyl]amino]butanoic acid (EC: 643-099-1)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/176125
    4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide Monohydrate (EC: 691-652-0)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/224992
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  8. ChEBI
  9. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. LiverTox
  11. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  12. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  13. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  14. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  15. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  16. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  17. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  18. Therapeutic Target Database (TTD)
  19. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  20. DailyMed
  21. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  23. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    BOSENTAN
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  24. Drugs and Lactation Database (LactMed)
  25. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  26. EU Clinical Trials Register
  27. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  28. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  29. FDA Medication Guides
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  30. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  31. Japan Chemical Substance Dictionary (Nikkaji)
  32. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  33. MassBank Europe
  34. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  35. Metabolomics Workbench
  36. Natural Product Activity and Species Source (NPASS)
  37. NIPH Clinical Trials Search of Japan
  38. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  39. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  40. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  41. Protein Data Bank in Europe (PDBe)
  42. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  43. Springer Nature
  44. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  45. Wikidata
  46. Wikipedia
  47. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    Endothelin Receptor Antagonists
    https://www.ncbi.nlm.nih.gov/mesh/68065128
  48. PubChem
  49. GHS Classification (UNECE)
  50. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  51. PATENTSCOPE (WIPO)
  52. NCBI
CONTENTS