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

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H24O5
Molecular Weight 284.3486
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARTENIMOL

SMILES

C[C@]1([H])CC[C@@]2([H])[C@@]([H])(C)[C@@]([H])(O)O[C@@]3([H])[C@]42[C@@]1([H])CC[C@](C)(O3)OO4

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 284.3486
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

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).

CNS Activity

Curator's Comment:: Dihydroartemisinin might accumulate in CSF during frequent artesunate dosing.

Originator

Sources: Kexue Tongbao (Chinese Edition) (1979), 24, (14), 667-9.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.5 nM [EC50]
Conditions

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.
PubMed

PubMed

TitleDatePubMed
Clinical review: Severe malaria.
2003 Aug
Comparison of bioassay and high performance liquid chromatographic assay of artesunate and dihydroartemisinin in plasma.
2003 Aug
Effect of dihydroartemisinin on the antioxidant capacity of P. falciparum-infected erythrocytes.
2003 Dec
A sensitive and selective liquid chromatographic/electrospray ionization tandem mass spectrometric assay for the simultaneous quantification of alpha-,beta-arteether and its metabolite dihydroartemisinin in plasma, useful for pharmacokinetic studies.
2003 Jul
Measurement of piperaquine in plasma by liquid chromatography with ultraviolet absorbance detection.
2003 Jul 5
Comparative clinical trial of two-fixed combinations dihydroartemisinin-napthoquine-trimethoprim (DNP) and artemether-lumefantrine (Coartem/Riamet) in the treatment of acute uncomplicated falciparum malaria in Thailand.
2003 Jun
Spectrophotometric and ESI-MS/HPLC studies reveal a common mechanism for the reaction of various artemisinin analogues with hemin.
2003 Nov 17
An HPLC-MS method for simultaneous estimation of alpha,beta-arteether and its metabolite dihydroartemisinin, in rat plasma for application to pharmacokinetic study.
2003 Oct
Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro.
2003 Sep
Protein binding and alpha : beta anomer ratio of dihydroartemisinin in vivo.
2004 Apr
Design of a dissolution system for the evaluation of the release rate characteristics of artemether and dihydroartemisinin from tablets.
2004 Apr 15
Activity of dihydroartemisinin against Leishmania donovani both in vitro and vivo.
2004 Aug
Development of a reversed-phase thin-layer chromatographic method for artemisinin and its derivatives.
2004 Aug
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
Pharmacokinetic investigation on the therapeutic potential of artemotil (beta-arteether) in Thai patients with severe Plasmodium falciparum malaria.
2004 Dec
A histidine-rich protein 2-based malaria drug sensitivity assay for field use.
2004 Dec
Comparison of the bioequivalence of three oral formulations of dihydroartemisinin based on ex vivo blood schizontocidal activities against Plasmodium falciparum.
2004 Dec
CV8, a new combination of dihydroartemisinin, piperaquine, trimethoprim and primaquine, compared with atovaquone-proguanil against falciparum malaria in Vietnam.
2004 Feb
Population pharmacokinetics of artemether and dihydroartemisinin following single intramuscular dosing of artemether in African children with severe falciparum malaria.
2004 Feb
Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria.
2004 Jan
Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers.
2004 Jul
Artemisinin induces apoptosis in human cancer cells.
2004 Jul-Aug
Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria.
2004 Mar
Antimalarial dihydroartemisinin also inhibits angiogenesis.
2004 May
Association of house spraying with suppressed levels of drug resistance in Zimbabwe.
2004 Oct 18
The pharmacokinetics of oral dihydroartemisinin and artesunate in healthy Thai volunteers.
2004 Sep
Experimental designed optimisation and stability evaluation of dry suspensions with artemisinin derivatives for paediatric use.
2004 Sep 28
Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers.
2005
[Review of the use of artemisinin and its derivatives in the treatment of malaria].
2005
In vitro antimalarial drug susceptibility in Thai border areas from 1998-2003.
2005 Aug 2
Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo.
2005 Dec 1
Development and validation of a high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydroartemisinin in human plasma.
2005 Feb 25
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
Yeast model uncovers dual roles of mitochondria in action of artemisinin.
2005 Sep
The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents.
2005 Sep
Pharmacokinetics of the diastereomers of arteether, a potent antimalarial drug, in rats.
2005 Sep
Concurrence of Plasmodium falciparum dhfr and crt mutations in northern Ghana.
2005 Sep 15
From artemisinin to new artemisinin antimalarials: biosynthesis, extraction, old and new derivatives, stereochemistry and medicinal chemistry requirements.
2006
[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
In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda.
2006 Jun
Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance.
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

Patents

Sample Use Guides

Eurartesim should be administered over three consecutive days for a total of three doses taken at the same time each day. Dosing should be based on body weight: 5 to <7kg -- ½ tablet (20 mg artenimol) per dose; 7 to <13 -- 1 tablet (20 mg artenimol) per dose; 13 to <24 – 1 tablet (40 mg artenimol) per dose; 24 to <36 -- 2 tablet (40 mg) per dose; 36 to <75 – 3 tablet (40 mg) per dose; 75 to 100 – 4 tablet (40 mg) per dose
Route of Administration: Oral
Thecytotoxicity of Artenimol in NCI cell line panel was measured by the sulforhodamine B assay. The cytotoxicity of Artenimol has been tested over a dose range from 10^−8 to 10^4 M in 60 tumor cell lines (CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226, SR, A549/ATCC, EKVX, HOP-62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCI-H522, COLO 205, HCC-2998, HCT-116, HCT-15, HT29, KM12, SW-620, SF-268, SF-295, SF-539, SNB-19, , SNB-75, U251, , LOX IMVI, MALME-3M, M14, MDA-MB-435, , SK-MEL-2, SK-MEL-28, SK-MEL-5, UACC-257, UACC-62, IGR-OV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/ADR-RES, , SK-OV-3, 786-0, A498, ACHN, CAKI-1, RXF 393, SN12C, TK-10, UO-31, PC-3, DU-145, MCF7, MDA-MB-231/ATCC, MDA-MB-468, HS 578T, MDA-N, Not Available, BT-549, T-47D).
Substance Class Chemical
Created
by admin
on Sat Jun 26 15:40:31 UTC 2021
Edited
by admin
on Sat Jun 26 15:40:31 UTC 2021
Record UNII
6A9O50735X
Record Status Validated (UNII)
Record Version
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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
DIHYDROARTEMISININ [WHO-DD]
Common Name English
ALAXIN
Brand Name English
SALAXIN
Common Name English
DIHYDROARTEMISININ [USP-RC]
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
COTECXIN
Brand Name English
DYNAMAX
Brand Name English
ARTENIMOL [WHO-DD]
Common 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
ARTENIMOL [WHO-IP]
Common Name English
Classification Tree Code System Code
WHO-ATC P01BF05
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
NCI_THESAURUS C271
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
WHO-ATC P01BE05
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
FDA ORPHAN DRUG 234006
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
EU-Orphan Drug EU/3/07/468
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
EMA ASSESSMENT REPORTS EURARTESIM (AUTHORIZED: MALARIA)
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
Code System Code Type Description
EVMPD
SUB30709
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
MESH
C039060
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
USP_CATALOG
1200520
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY USP-RS
DRUG BANK
DB11638
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
FDA UNII
6A9O50735X
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
CAS
71939-50-9
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
PUBCHEM
3000518
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ARTENIMOL
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
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.
INN
7777
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
WIKIPEDIA
DIHYDROARTEMISININ
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
MERCK INDEX
M2077
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
4194
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
NCI_THESAURUS
C87432
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
ChEMBL
CHEMBL252518
Created by admin on Sat Jun 26 15:40:32 UTC 2021 , Edited by admin on Sat Jun 26 15:40:32 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> METABOLITE ACTIVE
PARENT -> METABOLITE ACTIVE
MAJOR
PLASMA
PARENT -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY