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Esmolol

PubChem CID
59768
Structure
Esmolol_small.png
Esmolol_3D_Structure.png
Molecular Formula
Synonyms
  • ESMOLOL
  • 81147-92-4
  • 103598-03-4
  • (+-)-Esmolol
  • ASL 8052-001
Molecular Weight
295.37 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-18
Description
Methyl 3-{4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}propanoate is a methyl ester that is methyl 3-(4-hydroxyphenyl)propanoate in which the hydrogen attached to the phenolic hydroxy group is substituted by a 2-hydroxy-3-(isopropylamino)propyl group. It is an aromatic ether, a member of ethanolamines, a methyl ester, a secondary alcohol and a secondary amino compound. It is functionally related to a 3-{4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}propanoic acid.
Esmolol, commonly marketed under the trade name Brevibloc, is a cardioselective beta-1 receptor blocker. It has a rapid onset but short duration of action without causing significant intrinsic sympathomimetic or membrane stabilizing activities at recommended therapeutic doses. It works by blocking beta-adrenergic receptors in the heart, which leads to decreased force and rate of heart contractions. Esmolol prevents the action of two naturally occurring substances: epinephrine and norepinephrine. The FDA withdrew its approval for the use of all parenteral dosage form drug products containing esmolol hydrochloride that supply 250 milligrams/milliliter of concentrated esmolol per 10-milliliter ampule. Other esmolol formulations are still available for use.
Esmolol is a beta-Adrenergic Blocker. The mechanism of action of esmolol is as an Adrenergic beta-Antagonist.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Esmolol.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

methyl 3-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]propanoate
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C16H25NO4/c1-12(2)17-10-14(18)11-21-15-7-4-13(5-8-15)6-9-16(19)20-3/h4-5,7-8,12,14,17-18H,6,9-11H2,1-3H3
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

AQNDDEOPVVGCPG-UHFFFAOYSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

CC(C)NCC(COC1=CC=C(C=C1)CCC(=O)OC)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C16H25NO4
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

103598-03-4

2.3.3 Deprecated CAS

103598-03-4, 84057-94-3

2.3.4 European Community (EC) Number

2.3.5 UNII

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DrugBank ID

2.3.9 DSSTox Substance ID

2.3.10 HMDB ID

2.3.11 KEGG ID

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 Nikkaji Number

2.3.15 PharmGKB ID

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • ASL 8052
  • ASL-8052
  • Brevibloc
  • esmolol
  • esmolol hydrochloride

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
295.37 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3
Property Value
1.9
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
10
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
295.17835828 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
295.17835828 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
67.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
21
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
288
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
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
1
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

Very soluble as hydrochloride salt
1.44e-01 g/L

3.2.3 LogP

1.7
1.7

3.3 Chemical Classes

3.3.1 Drugs

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; Adrenergic Beta-Antagonists; Antiarrhythmics
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 2
Instrument Name
GC
Source of Spectrum
Chemical Concepts, A Wiley Division, Weinheim, Germany
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Technique
GC/MS
Source of Spectrum
H.H.Maurer, M.Meyer, K.Pfleger, A.A. Weber / University of Saarland, D-66424 Homburg Germany
Copyright
Copyright © 2023-2024 Wiley-VCH GmbH. All Rights Reserved.
Thumbnail
Thumbnail

4.1.2 MS-MS

1 of 3
View All
Spectra ID
Ionization Mode
positive
Top 5 Peaks

296.18927 100

297.190369 50.79

145.065689 36.79

219.102142 13.58

133.065323 7.04

Thumbnail
Thumbnail
Notes
instrument=qTof
2 of 3
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

296.18857 100

145.06563 62.74

219.1049 38.23

116.10717 18.27

98.09773 14.13

Thumbnail
Thumbnail

4.1.3 LC-MS

1 of 8
View All
Authors
Nihon Waters K.K.
Instrument
ZQ, Waters
Instrument Type
LC-ESI-Q
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ESI
Column Name
2.1 mm id - 3. 5{mu}m XTerra C18MS
Retention Time
12.420 min
Top 5 Peaks

105 999

115 960

103 787

118 646

107 627

Thumbnail
Thumbnail
License
CC BY-NC
2 of 8
View All
Authors
Nihon Waters K.K.
Instrument
ZQ, Waters
Instrument Type
LC-ESI-Q
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ESI
Column Name
2.1 mm id - 3. 5{mu}m XTerra C18MS
Retention Time
12.420 min
Top 5 Peaks

145 999

133 772

105 603

119 537

107 419

Thumbnail
Thumbnail
License
CC BY-NC

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable. Also used in noncompensatory sinus tachycardia where the rapid heart rate requires specific intervention.

7.2 LiverTox Summary

Esmolol is a cardioselective beta-blocker used in parenteral forms in the treatment of arrhythmias and severe hypertension. Esmolol has not been linked to instances of clinically apparent drug induced liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Adrenergic Beta-Antagonists; Antiarrhythmics
Beta-Adrenergic Receptor Antagonists

7.4 Drug Labels

Drug and label

7.5 Clinical Trials

7.5.1 ClinicalTrials.gov

7.5.2 EU Clinical Trials Register

7.5.3 NIPH Clinical Trials Search of Japan

8 Pharmacology and Biochemistry

8.1 MeSH Pharmacological Classification

Adrenergic beta-1 Receptor Antagonists
Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS. (See all compounds classified as Adrenergic beta-1 Receptor Antagonists.)

8.2 FDA Pharmacological Classification

FDA UNII
MDY902UXSR
Active Moiety
ESMOLOL
Pharmacological Classes
Mechanisms of Action [MoA] - Adrenergic beta-Antagonists
Pharmacological Classes
Established Pharmacologic Class [EPC] - beta-Adrenergic Blocker
FDA Pharmacology Summary
Esmolol is a beta-Adrenergic Blocker. The mechanism of action of esmolol is as an Adrenergic beta-Antagonist.

8.3 ATC Code

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

C07 - Beta blocking agents

C07A - Beta blocking agents

C07AB - Beta blocking agents, selective

C07AB09 - Esmolol

8.4 Absorption, Distribution and Excretion

Absorption
Rapidly absorbed, steady-state blood levels for dosages from 50-300 µg/kg/min (0.05-0.3 mg/kg/mm) are obtained within five minutes.
Route of Elimination
Consistent with the high rate of blood-based metabolism of esmolol hydrochloride, less than 2% of the drug is excreted unchanged in the urine. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. Excretion of the acid metabolite is significantly decreased in patients with renal disease, with the elimination half-life increased to about ten-fold that of normals, and plasma levels considerably elevated.
Clearance
20 L/kg/hr [Men]

8.5 Metabolism / Metabolites

Esmolol undergoes rapid hydrolysis of ester linkage which is catalyzed by esterases found in the cytosol of red blood cells (RBCs). The plasma cholinersterases or RBC membrane acetylcholinesterases are not involved in this metabolic reaction. Metabolism of the drug occurs mainly in RBCs to form a free acid metabolite (with 1/1500 the activity of esmolol) and methanol.

8.6 Biological Half-Life

Rapid distribution half-life of about 2 minutes and an elimination half-life of about 9 minutes. The acid metabolite has an elimination half-life of about 3.7 hours.

8.7 Mechanism of Action

Similar to other beta-blockers, esmolol blocks the agonistic effect of the sympathetic neurotransmitters by competing for receptor binding sites. Because it predominantly blocks the beta-1 receptors in cardiac tissue, it is said to be cardioselective. In general, so-called cardioselective beta-blockers are relatively cardioselective; at lower doses they block beta-1 receptors only but begin to block beta-2 receptors as the dose increases. At therapeutic dosages, esmolol does not have intrinsic sympathomimetic activity (ISA) or membrane-stabilizing (quinidine-like) activity. Antiarrhythmic activity is due to blockade of adrenergic stimulation of cardiac pacemaker potentials. In the Vaughan Williams classification of antiarrhythmics, beta-blockers are considered to be class II agents.

8.8 Human Metabolite Information

8.8.1 Cellular Locations

Membrane

8.8.2 Metabolite Pathways

9 Use and Manufacturing

9.1 Uses

Use (kg; approx.) in Germany (2009): >10

Use (kg) in USA (2002): 423

Consumption (g per capita; approx.) in Germany (2009): 0.000122

Consumption (g per capita) in the USA (2002): 0.0015

Calculated removal (%): 46.6

9.1.1 Use Classification

Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+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
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

11 Toxicity

11.1 Toxicological Information

11.1.1 Hepatotoxicity

Esmolol therapy has not been clearly associated with serum aminotransferase elevations or with clinically apparent, acute liver injury. It is often used in critically patients and generally for a short period only. Thus, hepatotoxicity due to esmolol must be very rare, if it occurs at all. Most commonly used beta-blockers have been linked to rare instances of clinically apparent liver injury, typically with onset within 2 to 12 weeks, a hepatocellular pattern of liver enzyme elevations, rapid recovery upon withdrawal, and little evidence of hypersensitivity (rash, fever, eosinophilia) or autoantibody formation. Similar instances have not been reported after esmolol use.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

11.1.2 Drug Induced Liver Injury

Compound
esmolol
DILI Annotation
No-DILI-Concern
Label Section
No match
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

No published information is available on the use esmolol during breastfeeding. Based on its physicochemical properties and extremely short half-life, esmolol would not be expected to cause any adverse effects in breastfed infants.

◉ Effects in Breastfed Infants

A study of mothers taking beta-blockers during nursing found a numerically, but not statistically significant increased number of adverse reactions in those taking any beta-blocker. Although the ages of infants were matched to control infants, the ages of the affected infants were not stated. None of the mothers were taking esmolol.

◉ Effects on Lactation and Breastmilk

Relevant published information on the effects of beta-blockade or esmolol during normal lactation was not found as of the revision date. A study in 6 patients with hyperprolactinemia and galactorrhea found no changes in serum prolactin levels following beta-adrenergic blockade with propranolol.

11.1.4 Protein Binding

55% bound to human plasma protein, while the acid metabolite is 10% bound.

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 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

15.2 Drug-Drug Interactions

15.3 Pathways

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 KEGG: ATC

17.5 KEGG: Target-based Classification of Drugs

17.6 KEGG: Drug Groups

17.7 WHO ATC Classification System

17.8 FDA Pharm Classes

17.9 ChemIDplus

17.10 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

17.11 ChEMBL Target Tree

17.12 UN GHS Classification

17.13 NORMAN Suspect List Exchange Classification

17.14 EPA DSSTox Classification

17.15 MolGenie Organic Chemistry Ontology

18 Information Sources

  1. CAS Common Chemistry
    LICENSE
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    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
    Methyl 3[4-[2-Hydroxy-3-(Isopropylamino)Propoxy]Phenyl] Propionate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.157.881
    Methyl 3[4-[2-Hydroxy-3-(Isopropylamino)Propoxy]Phenyl] Propionate (EC: 629-713-0)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/162597
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  8. ChEBI
    Methyl 3-{4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}propanoate
    https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:88206
  9. FDA Pharm Classes
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. LiverTox
  11. Open Targets
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    https://platform-docs.opentargets.org/licence
  12. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  13. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  14. DailyMed
  15. 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
  16. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  17. Therapeutic Target Database (TTD)
  18. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  19. Drugs and Lactation Database (LactMed)
  20. 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/
    ESMOLOL
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  21. EU Clinical Trials Register
  22. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  23. Japan Chemical Substance Dictionary (Nikkaji)
  24. KEGG
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    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
  25. MassBank Europe
  26. MassBank of North America (MoNA)
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
  27. Metabolomics Workbench
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  29. NIPH Clinical Trials Search of Japan
  30. NLM RxNorm Terminology
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  31. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  32. PharmGKB
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    https://www.pharmgkb.org/page/policies
  33. Pharos
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    https://pharos.nih.gov/about
  34. SpectraBase
  35. Springer Nature
  36. Thieme Chemistry
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    https://www.nlm.nih.gov/copyright.html
    Adrenergic beta-1 Receptor Antagonists
    https://www.ncbi.nlm.nih.gov/mesh/68058671
  41. GHS Classification (UNECE)
  42. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  43. PATENTSCOPE (WIPO)
  44. NCBI
CONTENTS