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

Details

Stereochemistry ABSOLUTE
Molecular Formula C16H26O5
Molecular Weight 298.3746
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARTEMETHER

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

InChIKey=SXYIRMFQILZOAM-HVNFFKDJSA-N
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

HIDE SMILES / InChI

Molecular Formula C16H26O5
Molecular Weight 298.3746
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://nutritionaloncology.org/Artemisinin.html http://www.druginfosys.com/drug.aspx?drugcode=1429&type=1 https://www.ncbi.nlm.nih.gov/pubmed/27006895

Artenimol (also known as dihydroqinghaosu, dihydroartemisinin or DHA) is the active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as a drug used to treat malaria. The proposed mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producing free radicals (hypervalent iron-oxo species, epoxides, aldehydes, and dicarbonyl compounds) which damage biological macromolecules causing oxidative stress in the cells of the parasite. Malaria is caused by apicomplexans, primarily Plasmodium falciparum, which largely reside in red blood cells and itself contains iron-rich heme-groups (in the form of hemozoin). Recent mechanism research discovered that artemisinin targets a broad spectrum of proteins in the human cancer cell proteome through heme-activated radical alkylation. Dihydroartemisinin is used to treat malaria, generally as a combination drug with piperaquine. In a systematic review of randomized controlled trials, both dihydroartemisinin-piperaquine and artemether-lumefantrine are very effective at treating malaria (high-quality evidence). However, dihydroartemisinin-piperaquine cures slightly more patients than artemether-lumefantrine, and it also prevents further malaria infections for longer after treatment (high-quality evidence). Dihydroartemisinin-piperaquine and artemether-lumefantrine probably have similar side effects (moderate-quality evidence). The studies were all conducted in Africa. In studies of people living in Asia, dihydroartemisinin-piperaquine is as effective as artesunate plus mefloquine at treating malaria (moderate-quality evidence). Artesunate plus mefloquine probably causes more nausea, vomiting, dizziness, sleeplessness, and palpitations than dihydroartemisinin-piperaquine (moderate-quality evidence).

Originator

Sources: Kexue Tongbao (Chinese Edition) (1979), 24, (14), 667-9.https://www.ncbi.nlm.nih.gov/pubmed/21989013
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

4.7329919E11
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

1.23906241E12
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
Inhibition of growth of Toxoplasma gondii by qinghaosu and derivatives.
1990 Oct
Extraction of artemisinin and artemisinic acid: preparation of artemether and new analogues.
1994 Jun
Demonstrating the validity of natural products as anti-infective drugs.
2001
Gas concentration effects on secondary metabolite production by plant cell cultures.
2001
Dodgy malaria drugs.
2001 Aug
In vivo-in vitro model for the assessment of clinically relevant antimalarial cross-resistance.
2001 Dec
Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy?
2001 Dec
Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites.
2001 Dec
New trends in extraction, identification and quantification of artemisinin and its derivatives.
2001 Dec
Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action.
2001 Dec
The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars.
2001 Dec
Redox reaction of artemisinin with ferrous and ferric ions in aqueous buffer.
2001 Dec
A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.
2001 Jul 15
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
Effects of matrine, artemisinin, tetrandrine on cytosolic [Ca2+]i in guinea pig ventricular myocytes.
2001 Jun
Frequency of early rising parasitemia in falciparum malaria treated with artemisinin derivatives.
2001 Mar
Effects of arteether on an auditory radial-arm maze task in rats.
2001 May
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
Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study.
2001 Nov 15
'To search and studdy out the secrett of tropical diseases by way of experiment'.
2001 Nov-Dec
Proposed reductive metabolism of artemisinin by glutathione transferases in vitro.
2001 Oct
Improved oral bioavailability of artemisinin through inclusion complexation with beta- and gamma-cyclodextrins.
2001 Oct 4
[Prevention and treatment of malaria: in vitro evaluation of new compounds].
2001 Sep
Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand.
2001 Sep 1
Epidemiology of drug-resistant malaria.
2002 Apr
Clinical status and implications of antimalarial drug resistance.
2002 Feb
Deoxyartemisinin derivatives from photooxygenation of anhydrodeoxydihydroartemisinin and their cytotoxic evaluation.
2002 Feb
Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance.
2002 Feb 10
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
Plasmodium falciparum: in vitro interactions of artemisinin with amodiaquine, pyronaridine, and chloroquine.
2002 Jan
Transmission electron microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether.
2002 Jan
Structure-activity relationships of the antimalarial agent artemisinin. 6. The development of predictive in vitro potency models using CoMFA and HQSAR methodologies.
2002 Jan 17
From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs.
2002 Mar
Inhibition of nitric oxide-dependent activation of soluble guanylyl cyclase by the antimalarial drug, artemisinin.
2002 Mar 1
First synthesis of 10 alpha-(trifluoromethyl)deoxoartemisinin.
2002 Mar 7
Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia.
2002 May
Central role of the spleen in malaria parasite clearance.
2002 May 15
Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells.
2002 May 28
Antimalarial drugs: QT prolongation and cardiac arrhythmias.
2005 May
In vitro inhibition of Toxoplasma gondii by four new derivatives of artemisinin.
2006 Dec
The clinical efficacy of artemether/lumefantrine (Coartem).
2009 Oct 12
Evaluation of drug effects on Toxoplasma gondii nuclear and plastid DNA replication using real-time PCR.
2010 Apr
Schistosoma mansoni: N-acetylcysteine downregulates oxidative stress and enhances the antischistosomal activity of artemether in mice.
2011 Jul
A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs.
2013 Dec 17
Use of artemether-lumefantrine to treat malaria during pregnancy: what do we know and need to know?
2013 Feb
Antimalarial activity of 10-alkyl/aryl esters and -aminoethylethers of artemisinin.
2013 Feb
Fetal bovine serum and human constitutive androstane receptor: evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system.
2014 Jun 1
Patents

Sample Use Guides

Tablets should be administered over 3 days for a total of 6 doses: an initial dose, second dose after 8 hours and then twice-daily (morning and evening) for the following 2 days. The adult dosage for patients with bodyweight of 35 kg and above is 4 tablets per dose for a total of 6 doses. Tablets are scored and contain 20 mg rtemether and 120 mg lumefantrine.
Route of Administration: Oral
In Vitro Use Guide
IC90 is higher in Plasmodium falciparum strain T-996 compared with strain LS-21: for artemether, 34.45 and 7.11 nmol/L (10.28 and 2.12 ng/ml of erythrocyte-medium mixture [EMM]).
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:09:13 UTC 2023
Edited
by admin
on Wed Jul 05 23:09:13 UTC 2023
Record UNII
C7D6T3H22J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ARTEMETHER
DASH   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP-RC   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
.BETA.-ARTEMETHER
Common Name English
NSC-665970
Code English
GVITHER
Common Name English
(+)-ARTEMETHER
Common Name English
ARTEMETHER [JAN]
Common Name English
COARTEM COMPONENT ARTEMETHER
Brand Name English
SM224
Code English
ARTEMETHER [MART.]
Common Name English
(3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-Methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano[4,3-j]-1,2-benzodioxepine
Common Name English
ARTEMETHERUM [WHO-IP LATIN]
Common Name English
MALARTEM
Common Name English
NSC-759820
Code English
(3R,5AS,6R,8AS,9R,10S,12R,12AR)-DECAHYDRO-10-METHOXY-3,6,9-TRIMETHYL-3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN
Systematic Name English
ARTEMETHER [HSDB]
Common Name English
ARTESAPH
Common Name English
LARITHER
Common Name English
ARTEMETHER [USAN]
Common Name English
FALCIDOL
Common Name English
PALUTHER
Common Name English
3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN, DECAHYDRO-10-METHOXY-3,6,9-TRIMETHYL-, (3R,5AS,6R,8AS,9R,10S,12R,12AR)-
Common Name English
ARTEMETHER [USP-RS]
Common Name English
Artemether [WHO-DD]
Common Name English
artemether [INN]
Common Name English
.BETA.-DIHYDROARTEMISININ METHYL ETHER
Common Name English
ARTEMETHER [MI]
Common Name English
ARTEMETHER [VANDF]
Common Name English
ARTEMETHER [WHO-IP]
Common Name English
ARTEMETHER COMPONENT OF COARTEM
Brand Name English
ARTEMETHER [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC P01BF01
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
NDF-RT N0000175482
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
FDA ORPHAN DRUG 245507
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
WHO-ATC P01BE02
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1 (ART/LUM)
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
EU-Orphan Drug EU/3/09/702
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
NCI_THESAURUS C271
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
Code System Code Type Description
FDA UNII
C7D6T3H22J
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
WIKIPEDIA
ARTEMETHER
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
PUBCHEM
68911
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
ChEMBL
CHEMBL566534
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
MESH
C032942
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
NSC
665970
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
RXCUI
18343
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY RxNorm
LACTMED
Artemether and Lumefantrine
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
EVMPD
SUB05574MIG
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
CHEBI
195280
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
DAILYMED
C7D6T3H22J
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
RS_ITEM_NUM
1042780
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
MERCK INDEX
M2075
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C73001
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
EPA CompTox
DTXSID7040651
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
DRUG BANK
DB06697
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
HSDB
7456
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ARTEMETHER
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY Description: White crystals or a white, crystalline powder. Solubility: Practically insoluble in water; very soluble in dichloromethane R and acetone R; freely soluble in ethyl acetate R and dehydrated ethanol R. Category: Antimalarial drug. Storage: Artemether should be kept in a tightly closed container and protected from light. Labelling: The designation Artemether for parenteral use indicates that the substance complies with the additional requirements and may be used for parenteral administration. Additional information: The parenteral form is normally intended for intramuscular administration. Requirement: Artemether contains not less than 97.0% and not more than the equivalent of 102.0% of C16H26O5 using ?Assay?, method A, andnot less than 98.0% and not more than the equivalent of 102.0% of C16H26O5 using ?Assay?, method B, both calculated with reference to the dried substance.
NSC
759820
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
USAN
UU-173
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
INN
6458
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
SMS_ID
100000092762
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
DRUG CENTRAL
245
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
CAS
71963-77-4
Created by admin on Wed Jul 05 23:09:13 UTC 2023 , Edited by admin on Wed Jul 05 23:09:13 UTC 2023
PRIMARY
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