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Artemether

July 24, 2017
Common Name

Artemether Description

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source (1R,4S,5R,8S,9R,10S,12R,13R)-10-Methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecaneChEBI 10-Methoxy-1,5,9-trimethyl-(1R,4S,5R,8S,9R,10S,12R,13R)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecaneChEBI ArtemeteroChEBI ArtemetherumChEBI Artemisininelactol methyl etherChEBI beta-ArtemetherChEBI beta-Dihydroartemisinin methyl etherChEBI Dihydroartemisinin methyl etherChEBI Methyl-dihydroartemisinineChEBI b-ArtemetherGenerator β-artemetherGenerator b-Dihydroartemisinin methyl etherGenerator β-dihydroartemisinin methyl etherGenerator

Chemical Formlia

C16H26O5 Average Molecliar Weight

298.3746 Monoisotopic Molecliar Weight

298.178023942 IUPAC Name

(1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0⁴,¹³.0⁸,¹³]hexadecane Traditional Name

artemether CAS Registry Number

71963-77-4 SMILES

[H][C@@]12CC[C@@H](C)[C@]3([H])CC[C@@]4(C)OO[C@@]13[C@]([H])(O[C@H](OC)[C@@H]2C)O4

InChI Identifier

InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1

InChI Key

SXYIRMFQILZOAM-HVNFFKDJSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as artemisinins. These are sesquiterpenoids originally isolated from the herb Artemisia annua. Their structure is based on artemisinin, a tetracyclic compound that contains a 1,2-dioxepane fused to an octahydrobenzopyran moiety. The internal peroxide bridge is believed to be a key to the mode of action of artemisinins. Kingdom

Chemical entities Super Class

Organic compounds Class

Lipids and lipid-like moleclies Sub Class

Prenol lipids Direct Parent

Artemisinins Alternative Parents

  • Oxepanes
  • Trioxanes
  • Oxanes
  • Dialkyl peroxides
  • Oxacyclic compounds
  • Acetals
  • Hydrocarbon derivatives

    • Substituents

  • Artemisinin skeleton
  • Oxepane
  • 1,2,4-trioxane
  • Oxane
  • Dialkyl peroxide
  • Oxacycle
  • Organoheterocyclic compound
  • Acetal
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic heteropolycyclic compound

    • Molecliar Framework

    Aliphatic heteropolycyclic compounds External Descriptors

  • semisynthetic derivative (CHEBI:195280 )
  • sesquiterpenoid (CHEBI:195280 )
  • artemisinin derivative (CHEBI:195280 )
  • cyclic acetal (CHEBI:195280 )
  • organic peroxide (CHEBI:195280 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antimalarial Agents
  • Antimalarials
  • Antiprotozoal Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point86 – 90 °CNot Available Boiling PointNot AvailableNot Available Water Solubility4.57e-01 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.46 mg/mLALOGPS logP3.02ALOGPS logP3.48ChemAxon logS-2.8ALOGPS pKa (Strongest Basic)-3.9ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area46.15 Å2ChemAxon Rotatable Bond Count1ChemAxon Refractivity74.66 m3·mol-1ChemAxon Polarizability32.12 Å3ChemAxon Number of Rings4ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-03di-0950000000-2ae4d4c9200a42ec883dView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Artemether Metabolism PathwaySMP00651Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06697

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06697

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB06697 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    62138 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Artemether NuGOwiki Link

    HMDB15643 Metagene Link

    HMDB15643 METLIN ID

    Not Available PubChem Compound

    68911 PDB ID

    Not Available ChEBI ID

    195280

    Product: Sodium Picosulfate

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Haynes RK, Vonwiller SC: Extraction of artemisinin and artemisinic acid: preparation of artemether and new analogues. Trans R Soc Trop Med Hyg. 1994 Jun;88 Suppl 1:S23-6. [PubMed:8053018 ]
    2. Makanga M, Krudsood S: The clinical efficacy of artemether/lumefantrine (Coartem). Malar J. 2009 Oct 12;8 Suppl 1:S5. doi: 10.1186/1475-2875-8-S1-S5. [PubMed:19818172 ]
    3. Mutabingwa TK, Adam I: Use of artemether-lumefantrine to treat malaria during pregnancy: what do we know and need to know? Expert Rev Anti Infect Ther. 2013 Feb;11(2):125-35. doi: 10.1586/eri.12.169. [PubMed:23409819 ]
    4. (). Artemether and Lumefantrine (2010). AHFS Drug Information [Electronic versionb]. Retrieved October 24, 2010.. .
    5. (). Artemether/Lumefantrine (2010). DrugPoints® System [Electronic version]. Retrieved October 24, 2010.. .
    6. (). Novartis. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2010 Feb.. .

    Enzymes

    General function:
    Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
    Gene Name:
    CYP2C9
    Uniprot ID:
    P11712
    Molecular weight:
    55627.365
    General function:
    Involved in monooxygenase 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 imipramine.
    Gene Name:
    CYP2C19
    Uniprot ID:
    P33261
    Molecular weight:
    55944.565
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    2. Elsherbiny DA, Asimus SA, Karlsson MO, Ashton M, Simonsson US: A model based assessment of the CYP2B6 and CYP2C19 inductive properties by artemisinin antimalarials: implications for combination regimens. J Pharmacokinet Pharmacodyn. 2008 Apr;35(2):203-17. doi: 10.1007/s10928-008-9084-6. Epub 2008 Mar 19. [PubMed:18350255 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
    Gene Name:
    CYP2B6
    Uniprot ID:
    P20813
    Molecular weight:
    56277.81
    References
    1. Elsherbiny DA, Asimus SA, Karlsson MO, Ashton M, Simonsson US: A model based assessment of the CYP2B6 and CYP2C19 inductive properties by artemisinin antimalarials: implications for combination regimens. J Pharmacokinet Pharmacodyn. 2008 Apr;35(2):203-17. doi: 10.1007/s10928-008-9084-6. Epub 2008 Mar 19. [PubMed:18350255 ]
    General function:
    Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
    Gene Name:
    CYP3A5
    Uniprot ID:
    P20815
    Molecular weight:
    57108.065

    PMID: 24152419

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