.ALPHA.-DIHYDROARTEMISININ

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

SMILES

C[C@@H]1CC[C@H]2[C@@H](C)[C@H](O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@@]23OO4

InChI

InChIKey=BJDCWCLMFKKGEE-KDTBHNEXSA-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	MOL RATIO 1 MOL RATIO (average)

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

Description

Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pneumocystis carinii 4	Inhibitor 8,504
Sodium/potassium-transporting ATPase subunit alpha-1 16	Inhibitor 8,504
Plasmodium falciparum 75	Inhibitor 8,504	4.1 nM [IC50]
Plasmodium yoelii 3	Inhibitor 8,504
Plasmodium berghei 9	Inhibitor 8,504
Plasmodium falciparum 75	Inhibitor 8,504
DNA 282	Binding Agent 1,076
DNA 282	Binding Agent 1,076
Plasmodium falciparum 75	Binding Agent 1,076

Conditions

Condition	Modality	Highest Phase	Product
Plasmodium falciparum malaria 63	Primary	Approved 8,583	Sodium artesunate
Plasmodium falciparum malaria 63	Curative	Approved 8,583	Eurartesim
Malaria 96	Curative	Approved 8,583	Unknown
Schistosoma mansoni infection 8	Curative	Phase III 665	Unknown
Colorectal cancer 102	Primary	Phase II 1,147	Unknown
Cervical cancer 40	Primary	Phase I 438	Unknown
Hepatocellular carcinoma 83	Primary	Phase I 438	Unknown
Breast cancer 432	Primary	Phase I 438	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.3 μg/mL	2.4 mg/kg multiple, intravenous		ARTESUNATE plasma	Homo sapiens
3.1 μg/mL	2.4 mg/kg multiple, intravenous		ARTENIMOL plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
0.7 μg × h/mL	2.4 mg/kg multiple, intravenous		ARTESUNATE plasma	Homo sapiens
3.5 μg × h/mL	2.4 mg/kg multiple, intravenous		ARTENIMOL plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.3 h	2.4 mg/kg multiple, intravenous		ARTESUNATE plasma	Homo sapiens
1.3 h	2.4 mg/kg multiple, intravenous		ARTENIMOL plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
7%	2.4 mg/kg multiple, intravenous		ARTESUNATE plasma	Homo sapiens
7%	2.4 mg/kg multiple, intravenous		ARTENIMOL plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
2.4 mg/kg 1 times / day multiple, intravenous Recommended	unhealthy, 1-72 years	Other AEs: Anemia, Transaminases increased...
100 mg 1 times / day multiple, oral Studied dose	unhealthy, 15-35 years	Other AEs: Nausea, Dizziness...
2.4 mg/kg 1 times / day multiple, intravenous\|oral Recommended	unhealthy, 2-87 years	Other AEs: Acute renal failure, Hemoglobinuria...
25 mg/kg 2 times / 3 weeks multiple, intravenous Highest studied dose	unhealthy, 58 years	DLT: Nausea, Vomiting...
18 mg/kg 2 times / 3 weeks multiple, intravenous MTD	unhealthy, 58 years	DLT: Hypersensitivity reaction...

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AEs

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AE	Significance	Dose	Population
Acute renal failure	10%	2.4 mg/kg 1 times / day multiple, intravenous Recommended	unhealthy, 1-72 years
Leukocytosis	10%	2.4 mg/kg 1 times / day multiple, intravenous Recommended	unhealthy, 1-72 years
Hyperbilirubinemia	14%	2.4 mg/kg 1 times / day multiple, intravenous Recommended	unhealthy, 1-72 years
Thrombocytopenia	18%	2.4 mg/kg 1 times / day multiple, intravenous Recommended	unhealthy, 1-72 years
Transaminases increased	27%	2.4 mg/kg 1 times / day multiple, intravenous Recommended	unhealthy, 1-72 years

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63918	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63918
eMolecules	1935656	https://www.emolecules.com/cgi-bin/more?vid=1935656
eMolecules	29933844	https://www.emolecules.com/cgi-bin/more?vid=29933844
eMolecules	31224737	https://www.emolecules.com/cgi-bin/more?vid=31224737
MolPort	MolPort-006-392-384	https://www.molport.com/shop/molecule-link/MolPort-006-392-384

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PubMed

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Title	Date	PubMed
Artesunate and mefloquine given simultaneously for three days via a prepacked blister is equally effective and tolerated as a standard sequential treatment of uncomplicated acute Plasmodium falciparum malaria: randomized, double-blind study in Thailand.	2002 Nov	12479545
Artesunate in the treatment of metastatic uveal melanoma--first experiences.	2005 Dec	16273263
Treatment of experimental nephrotic syndrome with artesunate.	2007 Jul-Aug	17661229
Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria.	2014 Jan 20	24443033
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.	2015 Jun	25752796

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Patents

Sample Use Guides

In Vivo Use Guide

Artesunate can be used orally, by intravenous or intramuscular injection or as a suppository. As an injection, artesunate 2.4mg/kg bw i.v or i.m. given on admission (time =0), then at 12hr and 24hr, then once a day.

Route of Administration: Other

In Vitro Use Guide

An artemisinin concentration of 100-300 nM in vitro caused swelling of the endoplasmic reticulum and mitochondria, as well as injuries both to the limiting and to the nuclear membranes of chloroquine-resistant P. falciparum (ItG2 strain) within 2 h.

Substance Class	Chemical
Record UNII	X0UIV26ABX
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN-10-OL, DECAHYDRO-3,6,9-TRIMETHYL-, (3R,5AS,6R,8AS,9R,10R,12R,12AR)-

Preferred Name

English

.ALPHA.-DIHYDROARTEMISININ

Common Name

English

DIHYDROARTIMISININ

Common Name

English

3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN-10-OL, DECAHYDRO-3,6,9-TRIMETHYL-, (3R-(3.ALPHA.,5A.BETA.,6.BETA.,8A.BETA.,9.ALPHA.,10.BETA.,12.BETA.,12AR*))-

Common Name

English

NSC-758682

Code

English

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Code System

Code

Type

Description

CAS

81496-81-3

PRIMARY

DRUG BANK

DBMET00793

PRIMARY

PUBCHEM

11358077

PRIMARY

FDA UNII

X0UIV26ABX

PRIMARY

RXCUI

2584841

PRIMARY

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Related Record

Type

Details


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Amount:

82 % (average)

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Related Record

Type

Details


					60W3249T9M

ARTESUNATE

PRODRUG -> METABOLITE ACTIVE

Comments:

ratio of alpha to beta DIHYDROARTEMISININ is 3.5

Qualification:

PLASMA

Amount:


					C7D6T3H22J

ARTEMETHER

PARENT -> METABOLITE

Amount:

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound