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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
Efficient preparations of the beta-glucuronides of dihydroartemisinin and structural confirmation of the human glucuronide metabolite.
2001 Apr 26
Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method.
2001 Dec
A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.
2001 May-Jun
Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells.
2001 Nov 21
[Study on treatment of multi-drug resistant falciparum malaria by using a combination of dihydroartemisinin and pyronaridine].
2002
Relative bioavailability of artesunate and dihydroartemisinin: investigations in the isolated perfused rat liver and in healthy Caucasian volunteers.
2002 Feb
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
Assessment of the neurotoxicity of oral dihydroartemisinin in mice.
2002 Jan-Feb
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
The future outlook of antimalarial drugs and recent work on the treatment of malaria.
2002 Jul-Aug
A comparative clinical trial of combinations of dihydroartemisinin plus azithromycin and dihydroartemisinin plus mefloquine for treatment of multidrug resistant falciparum malaria.
2002 Sep
The chemotherapy of rodent malaria. LX. The importance of formulation in evaluating the blood schizontocidal activity of some endoperoxide antimalarials.
2002 Sep
Molecular phylogeny of Subtribe Artemisiinae (Asteraceae), including Artemisia and its allied and segregate genera.
2002 Sep 26
Clinical review: Severe malaria.
2003 Aug
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
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
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
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
Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria.
2004 Mar
Antimalarial dihydroartemisinin also inhibits angiogenesis.
2004 May
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
Drug sensitivity of Plasmodium falciparum along the Thai-Myanmar border using the new field-deployable HRP2 in vitro assay.
2005
Artemisinin-based combination therapies for uncomplicated malaria.
2005 Feb 21
Synthesis and immunosuppressive activity of new artemisinin derivatives. 1. [12(beta or alpha)-Dihydroartemisininoxy]phen(ox)yl aliphatic acids and esters.
2005 Jul 14
[Dihydroartemisinin inhibits the expression of vascular endothelial growth factor in K562 cells].
2005 Nov
[Effect of dihydroartemisinin on ultrastructure of Giardia lamblia in vitro].
2005 Oct 30
The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents.
2005 Sep
[Synthesis and immunosuppressive activity of new artemisinin derivatives containing polyethylene glycol group].
2006 Jan
In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda.
2006 Jun
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
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MAJOR
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PARENT -> METABOLITE ACTIVE
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