Details of the Drug

General Information of Drug (ID: DMR27C8)

Drug Name

Artesunate

Synonyms

Arinate; Arsumax; Artesunato; Artesunatum; Artsuna; Dihydroqinghaosusuccinate; Nuartez; Plasmotrim; Plasmotrin; Qinghaozhi; Artesunic acid; Dihydroqinghasu hemsuccinate; Quinghaosu reduced succinate ester; Succinyl dihydroartemisinin; SM 804; WR 256283; Arsumax (TN); Artesunate (USAN); Artesunate (superseded RN); Artesunato [INN-Spanish]; Artesunatum [INN-Latin]; WR-256283; Dihydroartemisinine-12-alpha-succinate; Butanedioic acid, mono(decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin-10-yl) ester; Butanedioic acid, mono((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-yl) ester; (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, hydrogen succinate; 4-Oxo-4-(((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-3,12-epoxypyrano(4,3-j)-1,2-benzodioxepin-10-yl hydrogen butanedioate; 4-oxo-4-{[(3r,5as,6r,8as,9r,10r,12r,12ar)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl]oxy}butanoic acid; 4-oxo-4-{[(5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl]oxy}butanoic acid

Indication

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

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

384.4

Topological Polar Surface Area (xlogp)

2.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 0.7 mgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 3.3 mg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.5-15 min [2]
Clearance: The clearance of drug is 180 L/h [2]
Elimination: A dose of artesunate is 56.1% eliminated in the urine and 38.5% in the feces (in rats) [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 0.1 - 1.8 hours [2]
Metabolism: The drug is metabolized via plasma esterases [2]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 9.3645 micromolar/kg/day [3]
Unbound Fraction: The unbound fraction of drug in plasma is 0.25% [4]
Vd: The volume of distribution (Vd) of drug is 59.7 L [2]

Chemical Identifiers

Formula: C19H28O8
IUPAC Name: 4-oxo-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]butanoic acid
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(=O)CCC(=O)O)C
InChI: InChI=1S/C19H28O8/c1-10-4-5-13-11(2)16(23-15(22)7-6-14(20)21)24-17-19(13)12(10)8-9-18(3,25-17)26-27-19/h10-13,16-17H,4-9H2,1-3H3,(H,20,21)/t10-,11-,12+,13+,16-,17-,18-,19-/m1/s1
InChIKey: FIHJKUPKCHIPAT-AHIGJZGOSA-N

Cross-matching ID

PubChem CID: 6917864
ChEBI ID: CHEBI:63918
CAS Number: 88495-63-0
DrugBank ID: DB09274
TTD ID: D0D4JO
INTEDE ID: DR0143

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)	TTZVSJ2	NOUNIPROTAC	Inhibitor	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2A6 (CYP2A6)_{Main DME}	DEJVYAZ	CP2A6_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Accelerated clearance of Artesunate due to the transporter induction by Arn-509.	Acute myeloid leukaemia [2A60]	[16]
Ag-221	DMS0ZBI	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Ag-221.	BCR-ABL1-negative chronic myeloid leukaemia [2A41]	[17]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[18]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[19]
PF-04449913	DMSB068	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[16]
Revefenacin	DMMP5SI	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[20]
GS-9857	DMYU6P5	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by GS-9857.	Hepatitis virus infection [1E50-1E51]	[21]
Fostemsavir	DM50ILT	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[22]
Capmatinib	DMYCXKL	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Capmatinib.	Lung cancer [2C25]	[23]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[24]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[25]
Rucaparib	DM9PVX8	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Rucaparib.	Ovarian cancer [2C73]	[26]
Darolutamide	DMV7YFT	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[27]
Tedizolid	DMG2SKR	Moderate	Decreased clearance of Artesunate due to the transporter inhibition by Tedizolid.	Skin and skin-structure infection [1F28-1G0Z]	[16]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Artesunate caused by Pitolisant mediated induction of UGT.	Somnolence [MG42]	[16]
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⏷ Show the Full List of 15 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	FDA Approved Drug Products: Artesunate Intravenous Injection
3	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
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
6	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
7	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
8	Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
9	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
10	Psychotropic drug interactions with valproate. Clin Neuropharmacol. 2005 Mar-Apr;28(2):96-101.
11	The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
12	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
13	CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine delta-5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15.
14	Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms. J Biol Chem. 2001 Apr 6;276(14):10782-7.
15	Elucidation of the topography of the thapsigargin binding site in the sarco-endoplasmic calcium ATPase. Bioorg Med Chem. 2010 Aug 1;18(15):5634-46.
16	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17	Cerner Multum, Inc. "Australian Product Information.".
18	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
19	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
20	Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
21	Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir). Gilead Sciences, Foster City, CA.
22	Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
23	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
24	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
25	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
26	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
27	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.