Details of the Drug

General Information of Drug (ID: DMY4UMW)

Drug Name

Atovaquone

Synonyms

Acuvel; Atavaquone; Mepron; Pron; Wellvone; Atovaquone GlaxoSmithKline brand; Glaxo Wellcome brand of atovaquone; GlaxoSmithKline brand of atovaquone; Malarone Pediatric; BW 566C; BW 566C80; Hydroxynaphthoquinone 566C80; Atovaquone & Interleukin 12; BW 556C-80; BW 566C-80; BW-A 566C; DRG-0084; Hydroxynaphthoquinone, 566C80; Mepron (TN); Mepron (antipneumocystic); ATO & IL-12; Atovaquone (USP/INN); Atovaquone [USAN:BAN:INN]; CRL-8131 & Atovaquone; 2-(4-(4'-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone; 2-(4-(4-Chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone; 2-(trans-4-(4-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone; 2-(trans-4-(p-Chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone; 2-[trans-4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone; 2-[trans-4-(4-chlorophenyl)cyclohexyl]-3-hydroxynaphthalene-1,4-dione; 2-[trans-4-(p-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone; 3-(4-(4-chlorophenyl)cyclohexyl)-4-hydroxy-naphthalene-1,2-dione; 3-[4-(4-chlorophenyl)cyclohexyl]-4-hydroxynaphthalene-1,2-dione; 566C80 hydroxynaphthoquinone; 566C80, hydroxynaphthoquinone; ATQ

Indication

Disease Entry	ICD 11	Status	REF
Fungal infection	1F29-1F2F	Approved	[1]

Therapeutic Class

Antifungal Agents

Affected Organisms

Plasmodium

ATC Code

P01AX06: Atovaquone

P01AX: Other agents against amoebiasis and other protozoal diseases

P01A: AGENTS AGAINST AMOEBIASIS AND OTHER PROTOZOAL DISEASES

P01: ANTIPROTOZOALS

P: ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

366.8

Logarithm of the Partition Coefficient (xlogp)

5.2

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 4: low solubility and low permeability [2]
Clearance: The drug present in the plasma can be removed from the body at the rate of 0.15 mL/min/kg [3]
Elimination: 3% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.2 - 3.2 days [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 58.413 micromolar/kg/day [4]
Unbound Fraction: The unbound fraction of drug in plasma is 0.001% [3]
Vd: The volume of distribution (Vd) of drug is 0.6 +/- 0.17 L/kg []

Chemical Identifiers

Formula: C22H19ClO3
IUPAC Name: 3-[4-(4-chlorophenyl)cyclohexyl]-4-hydroxynaphthalene-1,2-dione
Canonical SMILES: C1CC(CCC1C2=CC=C(C=C2)Cl)C3=C(C4=CC=CC=C4C(=O)C3=O)O
InChI: InChI=1S/C22H19ClO3/c23-16-11-9-14(10-12-16)13-5-7-15(8-6-13)19-20(24)17-3-1-2-4-18(17)21(25)22(19)26/h1-4,9-13,15,24H,5-8H2
InChIKey: BSJMWHQBCZFXBR-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 74989
ChEBI ID: CHEMBL575568
CAS Number: 94015-53-9
UNII: Y883P1Z2LT
DrugBank ID: DB01117
TTD ID: D06ZEE
INTEDE ID: DR0158
ACDINA ID: D00849

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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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
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Fungal infection

ICD Disease Classification

1F29-1F2F

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.85E-01	2.24E-02	7.33E-02

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[8]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Atovaquone and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[9]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Cannabidiol.	Epileptic encephalopathy [8A62]	[10]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[11]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Atovaquone and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[12]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Atovaquone and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[13]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Atovaquone and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[14]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[15]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Idelalisib.	Mature B-cell leukaemia [2A82]	[16]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Atovaquone and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[10]


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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Benzyl alcohol	E00010	244	Antimicrobial preservative; Solvent
Saccharin sodium anhydrous	E00443	656582	Flavoring agent
Hypromellose	E00634	Not Available	Coating agent
Water	E00035	962	Solvent
Xanthan gum	E00694	Not Available	Bioadhesive material; Emulsifying agent; Gelling agent; Modified-release agent; Suspending agent; Viscosity-controlling agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Atovaquone 750mg/5ml suspension	750mg/5ml	Suspension	Oral

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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	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	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
5	Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42.
6	Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis. Eur J Clin Pharmacol. 2002 Apr;58(1):19-27.
7	Cerner Multum, Inc. "Australian Product Information.".
8	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
9	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
10	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
11	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
12	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
13	Canadian Pharmacists Association.
14	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
15	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
16	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.