Identification

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Name
Atovaquone
Accession Number
DB01117  (APRD00805)
Type
Small Molecule
Groups
Approved
Description

Atovaquone is a hydroxynaphthoquinone, or an analog of [ubiquinone], that has antimicrobial and antipneumocystis activity. It is being used in antimalarial protocols.

Structure
Thumb
Synonyms
  • 2-(trans-4-(p-Chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone
  • Atovacuona
  • Atovaquone
External IDs
566C / 566C80 / BW 566C / BW 566C-80 / DRG-0084
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MepronSuspension750 mgOralGlaxosmithkline Inc1996-09-10Not applicableCanada
MepronSuspension750 mg/5mLOralGlaxosmithkline Inc1995-02-282017-12-08Us
MepronSuspension750 mg/5mLOralCardinal Health1998-09-182014-08-31Us
MepronSuspension750 mg/5mLOralPhysicians Total Care, Inc.1995-02-282010-06-30Us
MepronSuspension750 mg/5mLOralGlaxoSmithKline LLC1998-09-18Not applicableUs
MepronTablet250 mg/1OralGlaxoSmithKline2007-01-092007-05-04Us
MepronSuspension750 mg/5mLOralGlaxoSmithKline LLC1995-02-28Not applicableUs
Mepron Tab 250mgTabletOralGlaxo Wellcome1993-12-311999-08-24Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-atovaquoneSuspensionOralApotex CorporationNot applicableNot applicableCanada
AtovaquoneSuspension750 mg/5mLOralLupin Pharmaceuticals, Inc.2018-11-07Not applicableUs
AtovaquoneSuspension750 mg/5mLOralPrasco Laboratories2014-03-20Not applicableUs
AtovaquoneSuspension750 mg/5mLOralNorthStar Rx LLC2019-03-01Not applicableUs
AtovaquoneSuspension750 mg/5mLOralVistapharm, Inc.2018-09-14Not applicableUs
AtovaquoneSuspension750 mg/5mLOralCamber Pharmaceuticals, Inc.2018-10-11Not applicableUs
AtovaquoneSuspension750 mg/5mLOralGlenmark Pharmaceuticals Inc., USA2017-12-31Not applicableUs
AtovaquoneSuspension750 mg/5mLOralAmneal Pharmaceuticals LLC2011-02-09Not applicableUs
Atovaquone Oral SuspensionSuspension750 mg/5mLOralKVK-Tech, Inc.2019-05-31Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Atovaquone and Proguanil HClAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralbryant ranch prepack2012-07-27Not applicableUs
Atovaquone and Proguanil HClAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralA-S Medication Solutions2012-07-27Not applicableUs
Atovaquone and Proguanil HClAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralPD-Rx Pharmaceuticals, Inc.2012-07-27Not applicableUs
Atovaquone and Proguanil HClAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralPrasco Laboratories2012-07-27Not applicableUs
Atovaquone and Proguanil HydrochlorideAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralSt. Mary's Medical Park Pharmacy2011-08-18Not applicableUs
Atovaquone and Proguanil HydrochlorideAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2013-01-23Not applicableUs54868 639320180907 15195 1dsruze
Atovaquone and Proguanil HydrochlorideAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralBluePoint Laboratories2014-03-13Not applicableUs
Atovaquone and Proguanil HydrochlorideAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralClinical Solutions2011-08-182017-06-23Us
Atovaquone and Proguanil HydrochlorideAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralDispensing Solutions, Inc.2011-08-18Not applicableUs68258 110420180907 15195 1u4lcab
Atovaquone and Proguanil HydrochlorideAtovaquone (250 mg/1) + Proguanil hydrochloride (100 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.2014-05-28Not applicableUs0378 416220180907 15195 1h2rmtg
International/Other Brands
Acuvel / Wellvone
Categories
UNII
Y883P1Z2LT
CAS number
95233-18-4
Weight
Average: 366.837
Monoisotopic: 366.102272181
Chemical Formula
C22H19ClO3
InChI Key
KUCQYCKVKVOKAY-CTYIDZIISA-N
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/h1-4,9-13,15,26H,5-8H2/t13-,15-
IUPAC Name
2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione
SMILES
OC1=C([C@H]2CC[C@@H](CC2)C2=CC=C(Cl)C=C2)C(=O)C2=CC=CC=C2C1=O

Pharmacology

Indication

For the treatment or prevention of Pneumocystis carinii pneumonia in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX). Also indicated for the acute oral treatment of mild to moderate PCP in patients who are intolerant to TMP-SMX.

Associated Conditions
Pharmacodynamics

Atovaquone is a highly lipophilic drug that closely resembles the structure [ubiquinone]. Its inhibitory effect being comparable to ubiquinone, atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis in atovaquone-responsive parasites. Cytochrome bc1 complex (complex III) seems to serve as a highly discriminating molecular target for atovaquone in Plasmodia. There is no significant risk for myelosuppression associated with atovaquone, making this drug a beneficial therapeutic agent for recipients of bone marrow transplantation.

Mechanism of action

The mechanism of action against Pneumocystis carinii has not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes. The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis. Atovaquone also has been shown to have good in vitro activity against Toxoplasma gondii.

TargetActionsOrganism
ACytochrome b
inhibitor
Plasmodium falciparum
ADihydroorotate dehydrogenase (quinone), mitochondrial
inhibitor
Plasmodium falciparum (isolate 3D7)
UDihydroorotate dehydrogenase (quinone), mitochondrial
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

The bioavailability of atovaquone is low and variable and is highly dependent on formulation and diet. Bioavailability of the suspension increases two-fold when administered with meals. When administered with food, bioavailability is approximately 47%. Without food, the bioavailability is 23%.

Volume of distribution
  • 0.60 ± 0.17 L/kg
Protein binding

Atovaquone is extensively bound to plasma proteins (99.9%) over the concentration range of 1 to 90 µg/mL.

Metabolism

Some evidence suggests limited metabolism (although no metabolites have been identified).

Route of elimination

The half-life of atovaquone is long due to presumed enterohepatic cycling and eventual fecal elimination. There was little or no excretion of atovaquone in the urine (less than 0.6%).

Half life

2.2 to 3.2 days

Clearance
  • 10.4 +/- 5.5 ml/min [HIV-infected patients receiving IV administration]
Toxicity

The median lethal dose is higher than the maximum oral dose tested in mice and rats (1825 mg/kg per day). Overdoses up to 31,500 mg of atovaquone have been reported. In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose.

Affected organisms
  • Plasmodium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Atovaquone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Atovaquone.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Atovaquone.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Atovaquone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Atovaquone.
AcepromazineThe risk or severity of QTc prolongation can be increased when Atovaquone is combined with Acepromazine.
AceprometazineThe risk or severity of QTc prolongation can be increased when Atovaquone is combined with Aceprometazine.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Atovaquone.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Atovaquone.
AcetophenazineThe risk or severity of QTc prolongation can be increased when Atovaquone is combined with Acetophenazine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
  • Fatty foods increase absorption.
  • Take with food, bioavailability is increased 2 to 3 fold.

References

Synthesis Reference
US5053432
General References
Not Available
External Links
Human Metabolome Database
HMDB0015249
KEGG Drug
D00236
KEGG Compound
C06835
PubChem Compound
74989
PubChem Substance
46507298
ChemSpider
10482034
BindingDB
16301
ChEBI
575568
ChEMBL
CHEMBL1450
Therapeutic Targets Database
DAP000156
PharmGKB
PA448502
HET
AOQ
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Atovaquone
ATC Codes
P01AX06 — Atovaquone
AHFS Codes
  • 08:30.92 — Miscellaneous Antiprotozoals
PDB Entries
4pd4
FDA label
Download (63 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
0RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1CompletedOtherPlasmodium Infections1
1CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii1
1CompletedPreventionMalaria caused by Plasmodium falciparum1
1CompletedPreventionPlasmodium Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) / PCP / Toxoplasmosis1
1, 2CompletedOtherPlasmodium Infections1
1, 2TerminatedTreatmentMalaria caused by Plasmodium falciparum1
2CompletedPreventionPlasmodium Infections1
2CompletedTreatmentBacterial Infections / Human Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
2CompletedTreatmentPlasmodium Infections1
2RecruitingTreatmentPlasmodium Infections1
2, 3CompletedTreatmentMalaria caused by Plasmodium falciparum1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii2
3CompletedTreatmentPlasmodium Falciparum Infection1
4Active Not RecruitingTreatmentPlasmodium Infections1
4CompletedNot AvailablePlasmodium Infections1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
4CompletedPreventionRabies1
4CompletedTreatmentFalciparum / Plasmodium Infections1
4CompletedTreatmentPlasmodium Infections1
4RecruitingTreatmentExercise / Pharmacokinetics1
4RecruitingTreatmentPlasmodium Falciparum Malaria (Drug Resistant)1
4WithdrawnTreatmentPneumonia, Pneumocystis Carinii1
Not AvailableCompletedBasic ScienceMalaria caused by Plasmodium falciparum1
Not AvailableCompletedBasic SciencePlasmodium Falciparum Malaria2
Not AvailableCompletedBasic SciencePlasmodium Falciparum / Plasmodium Infections1
Not AvailableCompletedBasic SciencePlasmodium Infections1
Not AvailableCompletedOtherControlled Human Malaria Infection / Gametocytes / Malaria caused by Plasmodium falciparum / Transmission1
Not AvailableCompletedPreventionPlasmodium Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii2
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
Not AvailableRecruitingPreventionControlled Human Malaria Infection / Immunization; Infection / Malaria caused by Plasmodium falciparum1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Cardinal Health
  • GlaxoSmithKline Inc.
  • Hetero Drugs Ltd.
  • Ivers Lee Division Of Jones Packaging Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
SuspensionOral
TabletOral
Tablet, film coatedOral
SuspensionOral750 mg
SuspensionOral750 mg/5mL
TabletOral250 mg/1
TabletOral
Prices
Unit descriptionCostUnit
Malarone 250-100 mg tablet7.7USD tablet
Mepron 750 mg/5 ml suspension4.95USD ml
Malarone 62.5-25 mg tablet4.33USD tablet
Mepron 150 mg/ml Suspension2.89USD ml
Malarone 62.5-25 mg ped tablet2.72USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6649659Yes2003-11-182017-01-10Us
US5998449No1999-12-072014-05-25Us
CA2152615No2001-10-162013-12-23Canada
CA2150234No2005-03-222013-11-25Canada
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP5.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000796 mg/mLALOGPS
logP4.74ALOGPS
logP5ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)5.53ChemAxon
pKa (Strongest Basic)-5.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity103.11 m3·mol-1ChemAxon
Polarizability39.64 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.5625
Caco-2 permeable+0.6239
P-glycoprotein substrateSubstrate0.536
P-glycoprotein inhibitor INon-inhibitor0.693
P-glycoprotein inhibitor IINon-inhibitor0.7554
Renal organic cation transporterNon-inhibitor0.7999
CYP450 2C9 substrateNon-substrate0.7986
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateNon-substrate0.5294
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5773
Ames testNon AMES toxic0.577
CarcinogenicityNon-carcinogens0.9067
BiodegradationNot ready biodegradable0.9922
Rat acute toxicity2.8010 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8511
hERG inhibition (predictor II)Non-inhibitor0.8037
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-066r-0968000000-4d83793ef10d849ce35e

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthoquinones. These are compounds containing a naphthohydroquinone moiety, which consists of a benzene ring linearly fused to a bezene-1,4-dione (quinone).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Naphthoquinones
Direct Parent
Naphthoquinones
Alternative Parents
Quinones / Aryl ketones / Chlorobenzenes / Aryl chlorides / Vinylogous acids / Enols / Organochlorides / Organic oxides / Hydrocarbon derivatives
Substituents
Naphthoquinone / Quinone / Aryl ketone / Chlorobenzene / Halobenzene / Aryl chloride / Monocyclic benzene moiety / Aryl halide / Vinylogous acid / Ketone
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
naphthoquinone, monochlorobenzenes (CHEBI:575568)

Targets

Kind
Protein
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Inhibitor
General Function
Oxidoreductase activity
Specific Function
Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis.
Gene Name
MT-CYB
Uniprot ID
Q02768
Uniprot Name
Cytochrome b
Molecular Weight
43376.225 Da
References
  1. Winter RW, Kelly JX, Smilkstein MJ, Dodean R, Hinrichs D, Riscoe MK: Antimalarial quinolones: synthesis, potency, and mechanistic studies. Exp Parasitol. 2008 Apr;118(4):487-97. Epub 2007 Nov 7. [PubMed:18082162]
  2. Cushion MT, Collins M, Hazra B, Kaneshiro ES: Effects of atovaquone and diospyrin-based drugs on the cellular ATP of Pneumocystis carinii f. sp. carinii. Antimicrob Agents Chemother. 2000 Mar;44(3):713-9. [PubMed:10681344]
  3. Kaneshiro ES: Are cytochrome b gene mutations the only cause of atovaquone resistance in Pneumocystis? Drug Resist Updat. 2001 Oct;4(5):322-9. [PubMed:11991686]
  4. Srivastava IK, Morrisey JM, Darrouzet E, Daldal F, Vaidya AB: Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Mol Microbiol. 1999 Aug;33(4):704-11. [PubMed:10447880]
  5. Syafruddin D, Siregar JE, Marzuki S: Mutations in the cytochrome b gene of Plasmodium berghei conferring resistance to atovaquone. Mol Biochem Parasitol. 1999 Nov 30;104(2):185-94. [PubMed:10593174]
  6. McFadden DC, Tomavo S, Berry EA, Boothroyd JC: Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance. Mol Biochem Parasitol. 2000 Apr 30;108(1):1-12. [PubMed:10802314]
  7. Kazanjian P, Armstrong W, Hossler PA, Lee CH, Huang L, Beard CB, Carter J, Crane L, Duchin J, Burman W, Richardson J, Meshnick SR: Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS. J Infect Dis. 2001 Mar 1;183(5):819-22. Epub 2001 Feb 1. [PubMed:11181161]
  8. Kessl JJ, Lange BB, Merbitz-Zahradnik T, Zwicker K, Hill P, Meunier B, Palsdottir H, Hunte C, Meshnick S, Trumpower BL: Molecular basis for atovaquone binding to the cytochrome bc1 complex. J Biol Chem. 2003 Aug 15;278(33):31312-8. Epub 2003 Jun 5. [PubMed:12791689]
  9. Kessl JJ, Ha KH, Merritt AK, Lange BB, Hill P, Meunier B, Meshnick SR, Trumpower BL: Cytochrome b mutations that modify the ubiquinol-binding pocket of the cytochrome bc1 complex and confer anti-malarial drug resistance in Saccharomyces cerevisiae. J Biol Chem. 2005 Apr 29;280(17):17142-8. Epub 2005 Feb 17. [PubMed:15718226]
  10. Meshnick SR, Berry EA, Nett J, Kazanjian P, Trumpower B: The interaction of atovaquone with the P. carinii cytochrome bc1 complex. J Eukaryot Microbiol. 2001;Suppl:169S-171S. [PubMed:11906048]
Kind
Protein
Organism
Plasmodium falciparum (isolate 3D7)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dihydroorotate dehydrogenase activity
Specific Function
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Gene Name
Not Available
Uniprot ID
Q08210
Uniprot Name
Dihydroorotate dehydrogenase (quinone), mitochondrial
Molecular Weight
65557.87 Da
References
  1. Cushion MT, Collins M, Hazra B, Kaneshiro ES: Effects of atovaquone and diospyrin-based drugs on the cellular ATP of Pneumocystis carinii f. sp. carinii. Antimicrob Agents Chemother. 2000 Mar;44(3):713-9. [PubMed:10681344]
  2. Ittarat I, Asawamahasakda W, Bartlett MS, Smith JW, Meshnick SR: Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase. Antimicrob Agents Chemother. 1995 Feb;39(2):325-8. [PubMed:7726490]
  3. Seymour KK, Lyons SD, Phillips L, Rieckmann KH, Christopherson RI: Cytotoxic effects of inhibitors of de novo pyrimidine biosynthesis upon Plasmodium falciparum. Biochemistry. 1994 May 3;33(17):5268-74. [PubMed:7909690]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquinone binding
Specific Function
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Gene Name
DHODH
Uniprot ID
Q02127
Uniprot Name
Dihydroorotate dehydrogenase (quinone), mitochondrial
Molecular Weight
42866.93 Da
References
  1. Knecht W, Henseling J, Loffler M: Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76. [PubMed:10658902]
  2. Hansen M, Le Nours J, Johansson E, Antal T, Ullrich A, Loffler M, Larsen S: 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. [PubMed:15044733]
  3. Ittarat I, Asawamahasakda W, Bartlett MS, Smith JW, Meshnick SR: Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase. Antimicrob Agents Chemother. 1995 Feb;39(2):325-8. [PubMed:7726490]
  4. Seymour KK, Lyons SD, Phillips L, Rieckmann KH, Christopherson RI: Cytotoxic effects of inhibitors of de novo pyrimidine biosynthesis upon Plasmodium falciparum. Biochemistry. 1994 May 3;33(17):5268-74. [PubMed:7909690]
  5. Seymour KK, Yeo AE, Rieckmann KH, Christopherson RI: dCTP levels are maintained in Plasmodium falciparum subjected to pyrimidine deficiency or excess. Ann Trop Med Parasitol. 1997 Sep;91(6):603-9. [PubMed:9425362]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data supporting this enzyme action are limited. Enzyme action is based on findings of in vitro studies. The inhibition of CYP2C9 is not expected to have clinically significant effects when substrates of this enzyme are coadministered.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Miller JL, Trepanier LA: Inhibition by atovaquone of CYP2C9-mediated sulphamethoxazole hydroxylamine formation. Eur J Clin Pharmacol. 2002 Apr;58(1):69-72. doi: 10.1007/s00228-002-0424-y. Epub 2002 Mar 7. [PubMed:11956677]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Manjunath P. Pai, Jennifer J. Kiser, Paul O. Gubbins, Keith A. Rodvold (2018). Drug Interactions in Infectious Diseases: Antimicrobial Drug Interactions (4th ed.). Springer. [ISBN:9783319724164]
  2. Piscitelli S., Rodvold K. and Pai M. (2011). Drug interactions in infectious diseases (3rd ed.). Springer Science. [ISBN:978-1-61779-212-0]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. van de Poll ME, Relling MV, Schuetz EG, Harrison PL, Hughes W, Flynn PM: The effect of atovaquone on etoposide pharmacokinetics in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2001 Jun;47(6):467-72. [PubMed:11459198]

Drug created on June 13, 2005 07:24 / Updated on December 06, 2019 11:54