U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H24O5
Molecular Weight 284.3481
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARTENIMOL

SMILES

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

InChI

InChIKey=BJDCWCLMFKKGEE-ISOSDAIHSA-N
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

HIDE SMILES / InChI

Molecular Formula C15H24O5
Molecular Weight 284.3481
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB06697 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy against malaria. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. Artemethe involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Other mechanisms of action for artemether include their ability to reduce fever by production of signals to hypothalamus thermoregulatory center. Now, recent research has shown the presence of a new, previously unknown cyclooxygenase enzyme COX-3, found in the brain and spinal cord, which is selectively inhibited by artemether, and is distinct from the two already known cyclooxygenase enzymes COX-1 and COX-2. It is now believed that this selective inhibition of the enzyme COX-3 in the brain and spinal cord explains the ability of artemether in relieving pain and reducing fever which is produced by malaria. The most common adverse reactions in adults (>30%) are headache, anorexia, dizziness, asthenia, arthralgia and myalgia.

CNS Activity

Curator's Comment: Meningeal inflammation increases artemether concentrations in cerebrospinal fluid in сhildrens treated with intramuscular artemether. http://aac.asm.org/content/55/11/5027.full

Originator

Sources: https://www.ncbi.nlm.nih.gov/pubmed/21989013Kexue Tongbao (Chinese Edition) (1979), 24, (14), 667-9.
Curator's Comment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778258/

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Eurartesim

Approved Use

Eurartesim is indicated for the treatment of uncomplicated Plasmodium falciparum malaria in adults, adolescents, children and infants 6 months and over and weighing 5 kg or more.
Curative
Eurartesim

Approved Use

Eurartesim is indicated for the treatment of uncomplicated Plasmodium falciparum malaria in adults, adolescents, children and infants 6 months and over and weighing 5 kg or more.
Curative
Artemisinin

Approved Use

Treatment of uncomplicated falciparum malaria in areas where there is evidence that chloroquine, pyrimethamine/sulfadoxine, mefloquine and quinine are ineffective. It should always be administered together with mefloquine in full therapeutic dose.

Launch Date

1984
Curative
COARTEM

Approved Use

Coartem (artemether/lumefantrine) Tablets are indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients of 5 kg bodyweight and above. Coartem Tablets have been shown to be effective in geographical regions where resistance to chloroquine has been reported [see Clinical Studies (14.1)

Launch Date

2009
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
60 ng/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
146 ng × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.6 h
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4.6%
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
80 mg 3 times / day multiple, oral
Recommended
Dose: 80 mg, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg, 3 times / day
Co-administed with::
lumefantrine, p.o(480 mg, b.i.d)
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Plasmodium falciparum malaria
Sources: Page: p.3
Disc. AE: QT interval prolonged...
AEs leading to
discontinuation/dose reduction:
QT interval prolonged
Sources: Page: p.3
80 mg 3 times / day multiple, oral
Recommended
Dose: 80 mg, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg, 3 times / day
Co-administed with::
lumefantrine, p.o(480 mg, b.i.d)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plasmodium falciparum malaria
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
QT interval prolonged Disc. AE
80 mg 3 times / day multiple, oral
Recommended
Dose: 80 mg, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg, 3 times / day
Co-administed with::
lumefantrine, p.o(480 mg, b.i.d)
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Plasmodium falciparum malaria
Sources: Page: p.3
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: administration of ketoconazole le to an increase in artemether (2.3-fold), dihydroartemisinin (1.5 fold), and lumefantrine (1.6-fold) exposure in healthy subjects;
Page: 14.0
minor
minor
minor
PubMed

PubMed

TitleDatePubMed
Gas concentration effects on secondary metabolite production by plant cell cultures.
2001
Systematic reviews of complementary therapies - an annotated bibliography. Part 2: herbal medicine.
2001
Severe falciparum malaria in five soldiers from East Timor: a case series and literature review.
2001 Aug
Artemisinin and derivatives: the future for malaria treatment?
2001 Dec
Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action.
2001 Dec
Redox reaction of artemisinin with ferrous and ferric ions in aqueous buffer.
2001 Dec
Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum.
2001 Dec 15
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.
2001 Jan
Antifungal activity of Artemisia annua endophyte cultures against phytopathogenic fungi.
2001 Jul 12
Rational use of drugs against Plasmodium falciparum.
2001 Jul-Aug
In vitro evidence for auto-induction of artemisinin metabolism in the rat.
2001 Jul-Sep
Drug resistant falciparum malaria: clinical consequences and strategies for prevention.
2001 Jun
Molecular cloning and characterization of peroxiredoxin from Toxoplasma gondii.
2001 Jun
Radical mechanism of action of the artemisinin-type compounds.
2001 Jun
Total synthesis of (+)-arteanniun M using the tandem oxy-Cope/ene reaction.
2001 Jun 14
Possible modes of action of the artemisinin-type compounds.
2001 Mar
Artemisinin and its derivatives: an important new class of antimalarial agents.
2001 May-Jun
Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro.
2001 May-Jun
In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs.
2001 Nov
In vitro beta-hematin formation assays with plasma of mice infected with Plasmodium yoelii and other parasite preparations: comparative inhibition with quinoline and endoperoxide antimalarials.
2001 Oct 26
Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand.
2001 Sep 1
Fourier transform infrared investigation of non-heme Fe(III) and Fe(II) decomposition of artemisinin and of a simplified trioxane alcohol.
2001 Sep 13
Deoxyartemisinin derivatives from photooxygenation of anhydrodeoxydihydroartemisinin and their cytotoxic evaluation.
2002 Feb
Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues.
2002 Feb 28
Alkylating capacity and reaction products of antimalarial trioxanes after activation by a heme model.
2002 Feb 8
Transmission electron microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether.
2002 Jan
In vitro antiprotozoal effects of artemisinin on Neospora caninum.
2002 Jan 3
Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma.
2002 Jul 15
Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua.
2002 Jun
Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?
2002 Mar 25
Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells.
2002 May 28
Characterization of noncovalent complexes of antimalarial agents of the artemisinin-type and FE(III)-heme by electrospray mass spectrometry and collisional activation tandem mass spectrometry.
2004 Aug
A histidine-rich protein 2-based malaria drug sensitivity assay for field use.
2004 Dec
Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers.
2005
Drug-resistant malaria in Bangui, Central African Republic: an in vitro assessment.
2005 Aug
Synthesis and immunosuppressive activity of new artemisinin derivatives. 1. [12(beta or alpha)-Dihydroartemisininoxy]phen(ox)yl aliphatic acids and esters.
2005 Jul 14
Toxicokinetics and hydrolysis of artelinate and artesunate in malaria-infected rats.
2005 Jul-Aug
Life-saving rectal artesunate for complicated malaria in children.
2005 May
In vitro interactions of Aspilia africana (Pers.) C.D. Adams, a traditional antimalarial medicinal plant, with artemisinin against Plasmodium falciparum.
2005 Nov 14
Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells.
2005 Nov-Dec
An open randomized clinical trial of Artekin vs artesunate-mefloquine in the treatment of acute uncomplicated falciparum malaria.
2005 Sep
Association of failures of seven-day courses of artesunate in a non-immune population in Bangui, Central African Republic with decreased sensitivity of Plasmodium falciparum.
2005 Sep
From artemisinin to new artemisinin antimalarials: biosynthesis, extraction, old and new derivatives, stereochemistry and medicinal chemistry requirements.
2006
Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro.
2006 Feb
[Synthesis and immunosuppressive activity of new artemisinin derivatives containing polyethylene glycol group].
2006 Jan
Manslaughter by fake artesunate in Asia--will Africa be next?
2006 Jun
Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance.
2006 May
Pharmacokinetics of piperaquine after repeated oral administration of the antimalarial combination CV8 in 12 healthy male subjects.
2006 May
Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria.
2006 May
The reaction of artemisinins with hemoglobin: a unified picture.
2006 May 1
Patents

Sample Use Guides

Adults and children: 25 mg/kg on the first day followed by 12.5 mg/kg on the second and third days in combination with mefloquine (15 mg/kg) in a single dose on the second day. In some areas, a higher dose (25 mg/kg) of mefloquine may be required for a cure to be obtained.
Route of Administration: Oral
In Vitro Use Guide
Artemisinine was active against 3 chloroquine-resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India, with complete growth inhibition at 10(-7) M.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:30:17 GMT 2023
Edited
by admin
on Sat Dec 16 16:30:17 GMT 2023
Record UNII
6A9O50735X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ARTENIMOL
INN   MART.   WHO-DD   WHO-IP  
INN  
Official Name English
ARTEMETHER RELATED COMPOUND A
USP-RS  
Common Name English
.BETA.-DIHYDROARTEMISININ
Common Name English
DIHYDROQINGHAOSU
Common Name English
ARTENIMOLUM [WHO-IP LATIN]
Common Name English
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)-
Common Name English
SANTECXIN
Brand Name English
EURARTESIM COMPONENT DIHYDROARTEMISININ
Brand Name English
DIHYDROARTEMISININ [USP-RS]
Common Name English
(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
Common Name English
DIHYDROARTEMISININ, .BETA.-
Common Name English
ALAXIN
Brand Name English
SALAXIN
Common Name English
(3R,5AS,6R,8AS,9R,10S,12R,12AR)-3,6,9-TRIMETHYLDECAHYDRO-3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN-10-OL
Systematic Name English
artenimol [INN]
Common Name English
DIHYDROARTEMISININ
Common Name English
DIHYDROARTEMISININ [MI]
Common Name English
Artenimol [WHO-DD]
Common Name English
COTECXIN
Brand Name English
DYNAMAX
Brand Name English
ARTENIMOL [MART.]
Common Name English
GNF-PF-5634
Code English
DIHYDROARTEMISININE
Common Name English
DI-HYDROQINGHAOSU
Common Name English
COTEXIN
Brand Name English
Dihydroartemisinin [WHO-DD]
Common Name English
ARTENIMOL [WHO-IP]
Common Name English
Classification Tree Code System Code
WHO-ATC P01BF05
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
NCI_THESAURUS C271
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
WHO-ATC P01BE05
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
FDA ORPHAN DRUG 234006
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
EU-Orphan Drug EU/3/07/468
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
EMA ASSESSMENT REPORTS EURARTESIM (AUTHORIZED: MALARIA)
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
Code System Code Type Description
EVMPD
SUB30709
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
SMS_ID
100000115442
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
MESH
C039060
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
DRUG BANK
DB11638
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
EPA CompTox
DTXSID501021652
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
FDA UNII
6A9O50735X
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
CAS
71939-50-9
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
PUBCHEM
3000518
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ARTENIMOL
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY Description: Colourless needles or a white or almost white, crystalline powder. Solubility: Practically insoluble in water; slightly soluble in acetonitrile R, ethanol (~750 g/l) TS and dichloromethane R. Category: Antimalarial. Storage: Artenimol should be kept in a well-closed container, protected from light. Definition: Artenimol contains not less than 97.0% and not more than the equivalent of 102.0% of C15H24O5 using Assay method A, and not less than 98.0% and not more than the equivalent of 102.0% of C15H24O5 using Assay method B, both calculated with reference to the dried substance.
RS_ITEM_NUM
1200520
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
INN
7777
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
WIKIPEDIA
DIHYDROARTEMISININ
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
MERCK INDEX
m2077
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY Merck Index
DRUG CENTRAL
4194
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
NCI_THESAURUS
C87432
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
ChEMBL
CHEMBL252518
Created by admin on Sat Dec 16 16:30:19 GMT 2023 , Edited by admin on Sat Dec 16 16:30:19 GMT 2023
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
PARENT -> DERIVATIVE
Related Record Type Details
PARENT -> METABOLITE ACTIVE
PRODRUG -> METABOLITE ACTIVE
PRODRUG -> METABOLITE ACTIVE
PARENT -> METABOLITE ACTIVE
Related Record Type Details
IMPURITY -> PARENT
PARENT -> IMPURITY
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY