Details of the Drug

General Information of Drug (ID: DM48QOT)

Drug Name

Artemether

Synonyms

Artemetero; Artemether[inn]; Artemetheri; Artemetherum; Artemos; Artenam; Artesaph; Artesian; Artimist; Artmether; Falcidol; Gvither; Malartem; Paluther; Rither; Arteannuin ether; Artemether [INN]; Artemisininelactol methyl ether; Dihydroartemisinin methyl ether; Dihydroquinghaosu methyl ether; SM 224; SM 229; Alpha-Artemether; Alpha-Dihydroartemisinin methyl ether; Artemetero [INN-Spanish]; Artemether (INN); Artemetherum [INN-Latin]; Beta-Artemether; Beta-Dihydroartemisinin methyl ether; Methyl-dihydroartemisinine; O-Methyldihydroartemisinine; SM-224; Beta-Methylether of 11-epi-dihydroartemisinin; Artemether, (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12beta,12aR*))-isomer; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano[4,3-j][1,2]benzodioxepine; (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; (3alpha,5abeta,6beta,8abeta,9alpha,10beta,12beta,12aR*)-isomer of artemether; (3r,5as,6r,8as,9r,10r,12r,12ar)-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isochromene; (5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isochromene; 10-methoxy-1,5,9-trimethyl-(1R,4S,5R,8S,9R,10S,12R,13R)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane; 3,12-Epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin, decahydro-10-methoxy-3,6,9-tri

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

298.37

Logarithm of the Partition Coefficient (xlogp)

3.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Bioavailability: 58% of drug becomes completely available to its intended biological destination(s) [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.2 +/- 1.9 hours [4]
Metabolism: The drug is metabolized to its active metabolite dihydroartemisinin []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 6.7028 micromolar/kg/day [5]

Chemical Identifiers

Formula: C16H26O5
IUPAC Name: (1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
Canonical SMILES: C[C@@H]1CC[C@H]2[C@H]([C@H](O[C@H]3[C@@]24[C@H]1CC[C@](O3)(OO4)C)OC)C
InChI: 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
InChIKey: SXYIRMFQILZOAM-HVNFFKDJSA-N

Cross-matching ID

PubChem CID: 68911
ChEBI ID: CHEBI:195280
CAS Number: 71963-77-4
DrugBank ID: DB06697
TTD ID: D0M9BW
INTEDE ID: DR0140

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium pump subunit alpha-1 (ATP1A1)	TTWK8D0	AT1A1_HUMAN	Binder	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[7]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[9]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[10]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Gene/Protein Processing	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Malaria

ICD Disease Classification

1F40-1F45

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Sodium pump subunit alpha-1 (ATP1A1)	DTT	ATP1A1	4.66E-01	1.00E-02	0.06
Sodium pump subunit alpha-1 (ATP1A1)	DTT	ATP1A1	3.31E-01	-0.03	-0.19
Cytochrome P450 2B6 (CYP2B6)	DME	CYP2B6	2.10E-02	9.95E-02	3.65E-01
Cytochrome P450 2B6 (CYP2B6)	DME	CYP2B6	2.07E-03	-2.31E-01	-5.10E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	6.74E-01	5.99E-02	7.30E-02
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	3.51E-01	1.59E-01	2.09E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	4.79E-03	1.32E-01	7.85E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	1.82E-01	-1.71E-02	-9.86E-02
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.01E-02	6.73E-02	3.36E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	2.91E-04	1.41E-01	6.14E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	7.33E-02	5.59E-02	2.99E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	5.65E-03	-7.28E-02	-1.24E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.13E-01	4.03E-02	2.50E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	8.21E-02	8.17E-02	4.35E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Artemether (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Major	Increased metabolism of Artemether caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[12]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Artemether caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[12]
Tucatinib	DMBESUA	Major	Decreased metabolism of Artemether caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[12]
Levonorgestrel	DM1DP7T	Moderate	Increased metabolism of Artemether caused by Levonorgestrel mediated induction of CYP450 enzyme.	Contraceptive management [QA21]	[13]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Artemether caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[14]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Artemether caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[15]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Artemether caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Artemether caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[16]
Boceprevir	DMBSHMF	Major	Decreased metabolism of Artemether caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[12]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Artemether caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Artemether caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[12]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Artemether caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[17]
Ceritinib	DMB920Z	Major	Decreased metabolism of Artemether caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[12]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Artemether caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[12]
Idelalisib	DM602WT	Major	Decreased metabolism of Artemether caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[12]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Artemether caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[18]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Artemether caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[19]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Artemether caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[20]
Enzalutamide	DMGL19D	Major	Increased metabolism of Artemether caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[12]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Artemether caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[19]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Artemether caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[21]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Artemether caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[12]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Artemether caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[12]
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⏷ Show the Full List of 23 DDI Information of This Drug

References

1	The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther. 1999 Oct;66(4):408-14.
7	The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects. Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):429-36.
8	Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9.
9	Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017 Jul 3;16(1):267.
10	Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
11	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. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):221-30. doi: 10.1016/j.taap.2014.03.023. Epub 2014 Apr 12.
12	Cerner Multum, Inc. "Australian Product Information.".
13	Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception.".
14	Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83. [PMID: 9834039]
15	EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
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17	Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):.
18	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
19	Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
20	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
21	Cerner Multum, Inc. "UK Summary of Product Characteristics.".