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Artenimol

PubChem CID
3000518
Structure
Artenimol_small.png
Artenimol_3D_Structure.png
Artenimol__Crystal_Structure.png
Molecular Formula
Synonyms
  • Dihydroartemisinin
  • Cotexin
  • 71939-50-9
  • Artenimol
  • Alaxin
Molecular Weight
284.35 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-08-01
  • Modify:
    2025-01-18
Description
Artenimol is an artemisinin derivative.
Artenimol is an artemisinin derivative and antimalarial agent used in the treatment of uncomplicated *Plasmodium falciparum* infections. It was first authorized for market by the European Medicines Agency in October 2011 in combination with [DB13941] as the product Eurartesim. Artemisinin combination therapy is highly effective against malaria and stongly recommended by the World Health Organization.
Alaxin has been reported in Ganoderma colossus and Acronychia pubescens with data available.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Artenimol.png

1.2 3D Conformer

1.3 Crystal Structures

CCDC Number
Associated Article
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C15H24O5/c1-8-4-5-11-9(2)12(16)17-13-15(11)10(8)6-7-14(3,18-13)19-20-15/h8-13,16H,4-7H2,1-3H3/t8-,9-,10+,11+,12+,13-,14-,15-/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

BJDCWCLMFKKGEE-ISOSDAIHSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[C@@H]1CC[C@H]2[C@H]([C@H](O[C@H]3[C@@]24[C@H]1CC[C@](O3)(OO4)C)O)C
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C15H24O5
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 Wikidata

2.3.13 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • (3R,5aS,6R,8aS,9R,10S,12R,12aR)-decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin-10-ol
  • 3alpha-hydroxydeoxydihydroartemisinin
  • 8alpha-hydroxydeoxyartemisinin
  • 9alpha-hydroxydeoxyartemisinin
  • Alaxin
  • artemisinin, dihydro-
  • artenimol
  • Cotecxin
  • Cotexin
  • dihydroartemisinin
  • dihydroartemisinine
  • dihydroqinghaosu
  • dihydroquinghaosu
  • dihydroquinghaosu, (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12alpha,12aR*))-isomer
  • dihydroquinghaosu, (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10beta,12alpha,12aR*))-isomer
  • quinghaosu, dihydro-
  • Salaxin
  • Santecxin

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
284.35 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
2.5
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
284.16237386 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
284.16237386 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
57.2 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
20
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
415
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
8
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 Melting Point

164-165
MSDS

3.2.2 Collision Cross Section

160.19 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

156.89 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

164.28 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

165.35 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 13C NMR Spectra

Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
Thumbnail
Thumbnail

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For the treatment of uncomplicated *Plasmodium falciparum* infection in adults, children, and infants aged 6 months and up weighing over 5 kg. Used in combination with [DB13941].

7.2 Clinical Trials

7.2.1 ClinicalTrials.gov

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Artenimol is thought to form a reactive carbon radical intermediate which kills *P. falciparum* through alkylation of a wide array of proteins.

8.2 MeSH Pharmacological Classification

Antimalarials
Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)

8.3 ATC Code

P - Antiparasitic products, insecticides and repellents

P01 - Antiprotozoals

P01B - Antimalarials

P01BE - Artemisinin and derivatives, plain

P01BE05 - Artenimol

8.4 Absorption, Distribution and Excretion

Absorption
The reported oral bioavailability of Artenimol was reported to be 45% in healthy adults. The observed Tmax was 1-2 h This is known to increase in malaria infected patients which could be attributed to reduced metabolism by the liver or the drug's collection in infected erythrocytes. Artenimol was obeserved to have flip-flop kinetics with an overall absorption half-life of 1.04 h. When administered with food the AUC for Artenimol increases by 144%. Cmax was observed to increase by 129% but was not found to be statistically significant. Food was observed to delay Tmax by 1 h.
Route of Elimination
Artenimol is eliminated via metabolism to glucuronide conjugates. There is little data on elimination of Artenimol but elimination of unchanged artemisinin compounds in feces and urine has been reported to be negligible.
Volume of Distribution

Artenimol was observed to have a mean apparent volume of distribution of 0.801 L/kg in adult patients and 0.705 L/kg in pediatric patients wit *P. falciparum

malaria.

Clearance

Artenimol was observed to have a mean apparent clearance of 1.340 L/h/kg in adult patients and 1.450 L/h/kg in pediatric patients with *P. falciparum

malaria.

8.5 Metabolism / Metabolites

The primary metabolite of Artenimol is the glucuronide conjugate, α-artenimol-β-glucuronide. It is largely metabolized by UGT1A9 with some contribution by UGT2B7.

8.6 Biological Half-Life

Artenimol was reported to have a half life of elimination of approximately 1 h.

8.7 Mechanism of Action

Artemisinins, including Artenimol which is a major active metabolite of many artemisinins, are thought to act via a common mechanism. While the exact mechanism of action is not certain, theories exist as to how artemisinins produce their antimalarial effect. Artemisinins are believed to bind to haem within the *P. falciparum* parasite. The source of this haem varies with the life stage of the parasite. When the parasite is in the early ring stage artemisinins are believed to bind haem produced by the parasite's haem biosynthesis pathway. In later stages artemisinins likely bind to haem released by haemoglobin digestion. Once bound to haem, artemisinins are thought to undergo activation involving ferrous iron via reductive scission which splits the endoperoxide bridge to produce a reactive oxygen. This reactive oxygen is thought to undergo a subsequent intramolecular hydrogen abstraction to produce a reactive carbon radical. The carbon radical is believed to be the source of the drugs potent activity against *P. falciparum* by alkylating a wide array of protein targets. The nature and magnitude of the effect on specific protein function as a result of this alkylation is unknown. One target which has been the focus of research is the sarco/endoplasmic reticulum Ca2+ ATPase pump of *P. falciparum*. Artemisinins have been found to irreversably bind to and inhibit this protein at a binding site similar to that of Thapsigargin. The mechanism is likely the same as for other proteins, namely alkylation via the carbon radical intermediate. Artemisinins appear to preferentially collect in infected erythrocytes, concentrating the drug by several hundred-fold compared to uninfected cells. This may play a role in why little alkylation is seen in uninfected erythrocytes.

9 Safety and Hazards

9.1 Hazards Identification

9.1.1 GHS Classification

Pictogram(s)
Flammable
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H242 (100%): Heating may cause a fire [Danger Self-reactive substances and mixtures; Organic peroxides]

H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P210, P234, P235, P240, P273, P280, P370+P378, P391, P403, P410, P411, P420, 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 2 reports by companies from 1 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.

9.1.2 Hazard Classes and Categories

Org. Perox. D (100%)

Aquatic Chronic 2 (100%)

9.2 Regulatory Information

REACH Registered Substance

10 Toxicity

10.1 Toxicological Information

10.1.1 Protein Binding

Artenimol has been reported to be 44-93% bound to plasma proteins. The identity of these proteins has not been reported.

11 Associated Disorders and Diseases

12 Literature

12.1 Consolidated References

12.2 NLM Curated PubMed Citations

12.3 Springer Nature References

12.4 Thieme References

12.5 Chemical Co-Occurrences in Literature

12.6 Chemical-Gene Co-Occurrences in Literature

12.7 Chemical-Disease Co-Occurrences in Literature

13 Patents

13.1 Depositor-Supplied Patent Identifiers

13.2 WIPO PATENTSCOPE

13.3 Chemical Co-Occurrences in Patents

13.4 Chemical-Disease Co-Occurrences in Patents

13.5 Chemical-Gene Co-Occurrences in Patents

14 Interactions and Pathways

14.1 Chemical-Target Interactions

14.2 Drug-Drug Interactions

15 Biological Test Results

15.1 BioAssay Results

16 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 WHO ATC Classification System

17.5 ChEMBL Target Tree

17.6 UN GHS Classification

17.7 NORMAN Suspect List Exchange Classification

17.8 CCSBase Classification

17.9 EPA DSSTox Classification

17.10 LOTUS Tree

17.11 EPA Substance Registry Services Tree

17.12 MolGenie Organic Chemistry Ontology

18 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. 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
  3. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  4. 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
    3,12-Epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-ol, decahydro-3,6,9-trimethyl-, (3R,5aS,6R,8aS,9R,10S,12R,12aR)-
    https://chem.echa.europa.eu/100.128.242
    3,12-Epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-ol, decahydro-3,6,9-trimethyl-, (3R,5aS,6R,8aS,9R,10S,12R,12aR)- (EC: 615-698-8)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/109214
  5. 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
  6. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  7. ChEBI
  8. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. Therapeutic Target Database (TTD)
  15. Japan Chemical Substance Dictionary (Nikkaji)
  16. 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
  17. Natural Product Activity and Species Source (NPASS)
  18. Metabolomics Workbench
  19. 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/
    Alpha-Dihydroartemisinin
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  20. SpectraBase
  21. Springer Nature
  22. The Cambridge Structural Database
  23. 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/
  24. 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/
  25. Wikidata
  26. Wikipedia
  27. PubChem
  28. 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
  29. GHS Classification (UNECE)
  30. EPA Substance Registry Services
  31. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  32. PATENTSCOPE (WIPO)
CONTENTS