Atovaquone

Summary

Atovaquone (CHEMBL1450) is an approved small-molecule antifungal agent (ATC P01AX06); indicated across 10 conditions including pneumocystosis and malaria.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: P01AX06
• Indications: 10 conditions
• Clinical trials: 30
• Chemistry: C22H19ClO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1450
Name	Atovaquone
Type	Small molecule
Max phase	4
ChEBI	CHEBI:575568
ATC	P01AX06
Molecular formula	C22H19ClO3
InChIKey	KUCQYCKVKVOKAY-CTYIDZIISA-N

SMILES: O=C1C(O)=C([C@H]2CC[C@H](c3ccc(Cl)cc3)CC2)C(=O)c2ccccc21

ChEBI definition: A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.

Pharmacological roles (ChEBI): antimalarial, antifungal agent, EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor, EC 1.6.5.3 [NADH:ubiquinone reductase (H+-translocating)] inhibitor, EC 1.10.2.2 (quinol—cytochrome-c reductase) inhibitor.

Also known as: 566C, 566C80, Atovacuona, Atovaquone, Atovaquone component of malarone, Mepron, NSC-759582, Wellvone, atovaquone, ATOVAQUONE, trans-Atovaquone, SID144204265

Patent coverage: 3,838 distinct patent families (14,589 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 14,480 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
	Plasmodium falciparum cytochrome b		9.52

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Dihydroorotate dehydrogenase (quinone), mitochondrial, Dihydroorotate dehydrogenase (quinone), mitochondrial, Broad substrate specificity ATP-binding cassette transporter ABCG2.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 6 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ABCG2	6.64	IC50	230	nM	CHEMBL_ACT_24777438
Q63707	6.16	IC50	700	nM	CHEMBL_ACT_12705563
DHODH	5.58	IC50	2600	nM	CHEMBL_ACT_19258668
DHODH	5.57	IC50	2700	nM	CHEMBL_ACT_19197976

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

10 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
pneumocystosis	4	MONDO:0019121	EFO:0007448
malaria	4	MONDO:0005136	EFO:0001068
amebiasis	4	MONDO:0005644	EFO:0007144
Plasmodium falciparum malaria	3	MONDO:0005920	EFO:0007444
cerebral toxoplasmosis	2	MONDO:0005697	EFO:0007200
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
non-small cell lung carcinoma	1	MONDO:0005233	EFO:0003060
gastroesophageal reflux disease	1	MONDO:0007186	EFO:0003948
acute myeloid leukemia	0	MONDO:0018874	EFO:0000222

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 30.

Phase distribution

Phase	Trials
PHASE2	7
Not specified	7
PHASE1	6
PHASE4	4
PHASE3	2
EARLY_PHASE1	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07357103	PHASE4	NOT_YET_RECRUITING	Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives)
NCT00421473	PHASE4	COMPLETED	Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients
NCT00451139	PHASE4	COMPLETED	Ototoxicity of Artemether / Lumefantrine (Coartem) and Other Antimalarials
NCT02564471	PHASE4	COMPLETED	Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis.
NCT00000802	PHASE3	COMPLETED	A Randomized, Comparative Study of Daily Dapsone and Daily Atovaquone for Prophylaxis Against PCP in HIV-Infected Patients Who Are Intolerant of Trimethoprim and/or Sulfonamides
NCT00002340	PHASE3	COMPLETED	A Comparison of Atovaquone and Pentamidine in the Prevention of Pneumocystis Carinii Pneumonia in HIV-Infected Patients Who Cannot Take TMP/SMX
NCT00084227	PHASE2/PHASE3	COMPLETED	Azithromycin Plus Chloroquine Versus Atovaquone-Proguanil For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In South America
NCT05998135	PHASE2	RECRUITING	Repurposing Atovaquone for the Treatment of Platinum-Resistant Ovarian Cancer
NCT00000655	PHASE2	COMPLETED	A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
NCT00000794	PHASE2	COMPLETED	Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
NCT00000811	PHASE2	COMPLETED	A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children
NCT00001996	PHASE2	COMPLETED	A Phase II Open Randomized Comparison of 566C80 and Pentamidine Isethionate for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients Who Are Intolerant of Trimethoprim / Sulfamethoxazole
NCT00984256	PHASE2	COMPLETED	Weekly Dosing of Malarone ® for Prevention of Malaria
NCT01442168	PHASE1/PHASE2	TERMINATED	Sevuparin/DF02 as an Adjunctive Therapy in Subjects Affected With Uncomplicated Falciparum Malaria
NCT04339426	PHASE2	TERMINATED	Atovaquone and Azithromycin Combination for Confirmed COVID-19 Infection
NCT06624371	PHASE1	RECRUITING	Atovaquone Combined With Radiation in Children With Malignant Brain Tumors
NCT00000773	PHASE1	COMPLETED	Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children
NCT01858831	PHASE1	COMPLETED	Single Oral Dose Study of Atovaquone/Proguanil Hydrochloride Combination Tablets and Atovaquone Suspension
NCT04568772	PHASE1	COMPLETED	Study to Evaluate the Influence of Tegoprazan on the Pharmacokinetics of Proguanil in Healthy Volunteers
NCT04648033	PHASE1	COMPLETED	Atovaquone With Radical ChemorADIotherapy in Locally Advanced NSCLC
NCT06294912	PHASE1	COMPLETED	A Study to Evaluate Antimalarial Activity and Safety of MK-7602 in Healthy Adults (MK-7602-003)
NCT02628080	EARLY_PHASE1	COMPLETED	Atovaquone as Tumour HypOxia Modifier
NCT03568994	EARLY_PHASE1	COMPLETED	Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML)
NCT00001990	Not specified	COMPLETED	An Open-Label, Uncontrolled Clinical Trial of Oral 566C80 for the Treatment of Patients With Severe PCP Who Are Intolerant and/or Unresponsive to Therapy With Trimethoprim/Sulfamethoxazole and Parenteral Pentamidine
NCT00001991	Not specified	COMPLETED	A Treatment IND for 566C80 Therapy of Pneumocystis Carinii Pneumonia
NCT00001994	Not specified	COMPLETED	A Pilot Study of 566C80 for the Salvage Treatment of Toxoplasmic Encephalitis in Patients Infected With the Human Immunodeficiency Virus (HIV) Who Have Failed or Are Intolerant of Pyrimethamine-Sulfadiazine
NCT02080026	Not specified	COMPLETED	Target Antigens Induced by Plasmodium Falciparum Sporozoite Immunization Under Chemoprophylaxis
NCT02098590	Not specified	COMPLETED	Chemoprophylaxis and Plasmodium Falciparum NF54 Sporozoite Immunization Challenged by Heterologous Infection
NCT03454048	Not specified	COMPLETED	Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2
NCT03813108	Not specified	TERMINATED	Safety and Efficacy of NF135 CPS Immunization

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).