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Details

Stereochemistry RACEMIC
Molecular Formula C18H26ClN3
Molecular Weight 319.8728
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHLOROQUINE

SMILES

CCN(CC)CCCC(C)Nc1ccnc2cc(ccc12)Cl

InChI

InChIKey=WHTVZRBIWZFKQO-UHFFFAOYSA-N
InChI=1S/C18H26ClN3/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21)

HIDE SMILES / InChI

Molecular Formula C18H26ClN3
Molecular Weight 319.8728
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Chloroquine (brand name Aralen) is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. In addition, chloroquine is in clinical trials as an investigational antiretroviral in humans with HIV-1/AIDS and as a potential antiviral agent against chikungunya fever. The mechanism of plasmodicidal action of chloroquine is not completely certain. However, is existed theory, that like other quinoline derivatives, it is thought to inhibit heme polymerase activity. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function.

CNS Activity

Curator's Comment:: Known to be CNS penetrant in rat. Human data not available.

Originator

Curator's Comment:: # Hans Andersag and coworkers at the Bayer laboratories

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
ARALEN

Approved Use

ARALEN is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. ARALEN does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

Launch Date

-636508800000
Curative
ARALEN

Approved Use

ARALEN is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. ARALEN does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

Launch Date

-636508800000
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
700 ng/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
134087 ng × h/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
209 h
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
45%
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3 g single, oral
Overdose
Dose: 3 g
Route: oral
Route: single
Dose: 3 g
Sources:
unknown, 14 years
Health Status: unknown
Age Group: 14 years
Sex: F
Sources:
Other AEs: Cardiac arrest...
Other AEs:
Cardiac arrest
Sources:
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Other AEs: Dizziness, Vomiting...
Other AEs:
Dizziness (19%)
Vomiting (17%)
Palpitations (5%)
Headache (6%)
Nausea (5%)
Abdominal pain (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Cardiac arrest
3 g single, oral
Overdose
Dose: 3 g
Route: oral
Route: single
Dose: 3 g
Sources:
unknown, 14 years
Health Status: unknown
Age Group: 14 years
Sex: F
Sources:
Vomiting 17%
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Dizziness 19%
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Abdominal pain 2%
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Nausea 5%
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Palpitations 5%
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Headache 6%
600 mg 2 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
Health Status: pregnant
Age Group: 20.7 years
Sex: F
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
yes [IC50 1096 uM]
yes [IC50 2.5 uM]
yes [Ki 12 uM]
weak (co-administration study)
Comment: selective inhibiton; Chloroquine produced a reduction in the metabolism of debrisoquine as evaluated by the debrisoquine recovery ratio, a measure of CYP2D6 activity. This reduction was progressive from the first to the seventh dose. This decrease in metabolism was modest (about 7% after the first dose and about 18% after seven doses) but statistically significant
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes (co-administration study)
Comment: Concomitant administration of a single dose of chloroquine and cimetidine daily starting 4 days prior to chloroquine, resulted in a 50% increase in chloroquine half-life, associated with a 50% decrease in its clearance.Since the AUC of desethylchloroquine decreased by 47%, cimetidine probably decreased chloroquine clearance by inhibiting its hepatic desethylation.
yes
yes (co-administration study)
Comment: Concomitant administration of a single dose of chloroquine and cimetidine daily starting 4 days prior to chloroquine, resulted in a 50% increase in chloroquine half-life, associated with a 50% decrease in its clearance.Since the AUC of desethylchloroquine decreased by 47%, cimetidine probably decreased chloroquine clearance by inhibiting its hepatic desethylation.
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
A Comparative Study of Hymenolepicides in Hymenolepis Mana Infestation of Rats.
1962 Jul
Tumor- and drug-induced cutaneous neuro-phospholipidosis.
1975
Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Central Asia.
1990
Inhibition of human immunodeficiency virus infectivity by chloroquine.
1990 Apr
Amrinone for refractory cardiogenic shock following chloroquine poisoning.
1991
Persisting chloroquine-induced myasthenia?
1991
Seizures associated with chloroquine therapy.
1992 Aug
Chloroquine related complete heart block with blindness: case report.
1992 Jan
Involvement of GABAergic mechanisms in chloroquine-induced seizures in mice.
1992 Mar
[Heart conduction disorders in long-term treatment with chloroquine. Two new cases].
1992 May 2-9
Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine.
2003 Feb 15
[Infectious diseases in 2003].
2004
The antimalarial potential of 4-quinolinecarbinolamines may be limited due to neurotoxicity and cross-resistance in mefloquine-resistant Plasmodium falciparum strains.
2004 Jul
Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells.
2004 Jul
Survival and surface adherence ability of bacterial pathogens in oral liquid pharmaceuticals and their containers.
2004 Jun
Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract.
2004 Jun 11
The multifocal pattern electroretinogram in chloroquine retinopathy.
2004 Mar-Apr
The ability of chloroquine to prevent tat-induced cytokine secretion by monocytes is implicated in its in vivo anti-human immunodeficiency virus type 1 activity.
2004 Nov
Attenuation of chloroquine-induced renal damage by alpha-lipoic acid: possible antioxidant mechanism.
2004 Sep
Seizure associated with chloroquine therapy in a patient with systemic lupus erythematosus.
2004 Sep
Chloroquine-induced cardiomyopathy-echocardiographic features.
2005 Apr
Skeletal muscle expression of clathrin and mannose 6-phosphate receptor in experimental chloroquine-induced myopathy.
2005 Apr
Enhanced anticryptococcal activity of chloroquine in phosphatidylserine-containing liposomes in a murine model.
2005 Feb
cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells.
2005 Feb 4
[Malaria chemoprophylaxis in traveling children].
2005 Jan
[Acute hydroxychloroquine poisoning. The danger of rapid or excessive correction of initial hypokalemia].
2005 Jul 23
Chloroquine-induced lipidosis mimicking Fabry disease.
2005 May
Ginkgo biloba leaf extract (EGb 761) enhances catalepsy induced by haloperidol and L-nitroarginine in mice.
2005 Nov
Protective effects of different antioxidants and amrinone on vancomycin-induced nephrotoxicity.
2005 Nov
Images in cardiovascular medicine. Contrast-enhanced magnetic resonance imaging of a patient with chloroquine-induced cardiomyopathy confirmed by endomyocardial biopsy.
2006 Aug 22
Selective enhancement of cellular oxidative stress by chloroquine: implications for the treatment of glioblastoma multiforme.
2006 Dec 15
CpG-B oligodeoxynucleotide promotes cell survival via up-regulation of Hsp70 to increase Bcl-xL and to decrease apoptosis-inducing factor translocation.
2006 Dec 15
[Complete auriculoventricular block secondary to cardiac toxicity due to chloroquine].
2006 Feb
[Cytochrome P-450 and the response to antimalarial drugs].
2006 Jan
Plasmodium berghei: development of an irreversible experimental malaria model in Wistar rats.
2006 Jul
Mefloquine toxicity presenting with polyneuropathy - a report of two cases in India.
2006 Jun
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients.
2006 Mar
Tetrahydrocurcumin: effect on chloroquine-mediated oxidative damage in rat kidney.
2006 Nov
Expression of autophagy-associated genes in skeletal muscle: an experimental model of chloroquine-induced myopathy.
2007
Cardiomyopathy related to antimalarial therapy with illustrative case report.
2007
[Complete auriculoventricular block during chloroquine treatment].
2007 Feb
Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.
2007 Jan 9
Effect of chloroquine on gene expression of Plasmodium yoelii nigeriensis during its sporogonic development in the mosquito vector.
2007 Jul 2
Chloroquine-induced recurrent psychosis.
2007 Jul-Aug
[Reversible restrictive cardiomyopathy secondary to chloroquine].
2007 Jun 23
Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases.
2007 May
Effects of CpG-B ODN on the protein expression profile of swine PBMC.
2007 Nov-Dec
A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru.
2007 Oct 31
Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine.
2008 Jul 4
Patents

Sample Use Guides

The dosage of chloroquine phosphate is often expressed in terms of equivalent
Route of Administration: Oral
Chloroquine inhibited mouse colon cancer cell line CT26 cells proliferation by concentration- and time-dependent manner. This effect was associated with apoptosis induction and decreased level of phosphorylated p42/44 mitogen-activated protein kinase and phosphorylated Akt. The cytotoxicity of chloroquine on CT26 cells was determined by the MTT assay. Cells were seeded in 96-well plates at the density of 2000/well and cultured for 24 hr, followed by chloroquine treatment (100, 50, 25, 12.5, 6.25, and 3.125 μ mol/L) for 24, 48, and 72 hr, respectively.
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:58:59 UTC 2021
Edited
by admin
on Fri Jun 25 20:58:59 UTC 2021
Record UNII
886U3H6UFF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CHLOROQUINE
HSDB   INN   MART.   MI   USP   VANDF   WHO-DD  
INN  
Official Name English
CHLOROQUINE [MI]
Common Name English
CHLOROQUINE [INN]
Common Name English
CHLOROQUINE [VANDF]
Common Name English
1,4-PENTANEDIAMINE, N(SUP 4)-(7-CHLORO-4-QUINOLINYL)-N(SUP 1),N (SUP 1)-DIETHYL-
Common Name English
7-CHLORO-4-((4-(DIETHYLAMINO)-1-METHYLBUTYL)AMINO)QUINOLINE
Systematic Name English
CHLOROQUINE [USP MONOGRAPH]
Common Name English
CHLOROQUINE [USP]
Common Name English
CHLOROQUINE [MART.]
Common Name English
CHLOROQUINE [WHO-DD]
Common Name English
NSC-187208
Code English
CHLOROQUINE [HSDB]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C271
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.5.3.2
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
LIVERTOX 193
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
EU-Orphan Drug EU/3/14/1377
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
CFR 21 CFR 522.810
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 2.4
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
IARC Chloroquine
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
FDA ORPHAN DRUG 475015
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
WHO-ATC P01BA01
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
NDF-RT N0000175482
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Code System Code Type Description
DRUG CENTRAL
607
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
CAS
54-05-7
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
NCI_THESAURUS
C61671
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
LACTMED
Chloroquine
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
DRUG BANK
DB00608
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
MERCK INDEX
M3435
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PRIMARY Merck Index
IUPHAR
5535
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
PUBCHEM
2719
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
INN
386
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PRIMARY
EVMPD
SUB06196MIG
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PRIMARY
WIKIPEDIA
CHLOROQUINE
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
FDA UNII
886U3H6UFF
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-191-2
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
HSDB
3029
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PRIMARY
RXCUI
2393
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PRIMARY RxNorm
EPA CompTox
54-05-7
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
MESH
D002738
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PRIMARY
ChEMBL
CHEMBL76
Created by admin on Fri Jun 25 20:59:00 UTC 2021 , Edited by admin on Fri Jun 25 20:59:00 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
ENANTIOMER -> RACEMATE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
BINDER->LIGAND
TARGET ORGANISM->INHIBITOR
In Vero E6 cells
EC50
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
ENANTIOMER -> RACEMATE
TARGET ORGANISM->INHIBITOR
Chloroquine resistant strains
IC50
TRANSPORTER -> INHIBITOR
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METABOLITE ACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC