HYDROXYCHLOROQUINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H26ClN3O
Molecular Weight	335.872
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CCO)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1

InChI

InChIKey=XXSMGPRMXLTPCZ-UHFFFAOYSA-N

InChI=1S/C18H26ClN3O/c1-3-22(11-12-23)10-4-5-14(2)21-17-8-9-20-18-13-15(19)6-7-16(17)18/h6-9,13-14,23H,3-5,10-12H2,1-2H3,(H,20,21)

HIDE SMILES / InChI

Molecular Formula	C18H26ClN3O
Molecular Weight	335.872
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.drugbank.ca/drugs/DB01611
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/009768s041lbl.pdf

Hydroxychloroquine possesses antimalarial properties and also exerts a beneficial effect in lupus erythematosus (chronic discoid or systemic) and acute or chronic rheumatoid arthritis. Although the exact mechanism of action is unknown, it may be based on ability of hydroxychloroquine to bind to and alter DNA. Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte. This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite. Its ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection. As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown. Hydroxychloroquine is used for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Toll-like receptor 7 13 Target ID: CHEMBL5936 Sources: http://www.drugbank.ca/drugs/DB01611	Antagonist 2849		2.78 µM [IC50]
Toll-like receptor 9 4 Target ID: CHEMBL5804 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24342772	Antagonist 2849		0.08 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Malaria 96 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/009768s041lbl.pdf	Curative	Approved 8583	PLAQUENIL Approved Use PLAQUENIL is indicated for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis. Launch Date 1955
Systemic lupus erythematosus 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/009768s041lbl.pdf	Primary	Approved 8583	PLAQUENIL Approved Use PLAQUENIL is indicated for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis. Launch Date 1955
Rheumatoid arthritis 320 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/009768s041lbl.pdf	Primary	Approved 8583	PLAQUENIL Approved Use PLAQUENIL is indicated for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis. Launch Date 1955

C_max

Value	Dose	Co-administered	Analyte	Population
50.3 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf	155 mg single, oral dose: 155 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYCHLOROQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
129.6 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf	155 mg single, oral dose: 155 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYCHLOROQUINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2500 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24991839/	465 mg 2 times / day multiple, oral dose: 465 mg route of administration: Oral experiment type: MULTIPLE co-administered: TEMOZOLOMIDE	TEMOZOLOMIDE	HYDROXYCHLOROQUINE blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.22 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19188392	310 mg single, oral dose: 310 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYCHLOROQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
102.3 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19188392	310 mg single, oral dose: 310 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYCHLOROQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2963 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf	155 mg single, oral dose: 155 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYCHLOROQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
537 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf	155 mg single, oral dose: 155 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYCHLOROQUINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
172.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19188392	310 mg single, oral dose: 310 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYCHLOROQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
48% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359187	unknown, unknown		HYDROXYCHLOROQUINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
12 g 1 times / day single, oral Studied dose Dose: 12 g, 1 times / day Route: oral Route: single Dose: 12 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	healthy, 16 years Health Status: healthy Age Group: 16 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	Other AEs: Cardio-respiratory arrest... Other AEs: Cardio-respiratory arrest (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/
200 mg 1 times / day single, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: single Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	healthy, 16 years Health Status: healthy Age Group: 16 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	Other AEs: Tachycardia, Hypotension... Other AEs: Tachycardia Hypotension Depression Hypokalemia Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/
20 g 1 times / day single, oral Studied dose Dose: 20 g, 1 times / day Route: oral Route: single Dose: 20 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	healthy, 18 years Health Status: healthy Age Group: 18 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	Other AEs: Hypotension, Hypokalemia... Other AEs: Hypotension Hypokalemia Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/
12 g 1 times / day single, oral Studied dose Dose: 12 g, 1 times / day Route: oral Route: single Dose: 12 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	healthy, 2.5 years Health Status: healthy Age Group: 2.5 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	Other AEs: Cardio-respiratory arrest... Other AEs: Cardio-respiratory arrest (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/
4 g 1 times / day single, oral Studied dose Dose: 4 g, 1 times / day Route: oral Route: single Dose: 4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	healthy, 29 years Health Status: healthy Age Group: 29 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/	Other AEs: Vomiting, Ventricular tachycardia... Other AEs: Vomiting Ventricular tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/11555803/
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: https://pubmed.ncbi.nlm.nih.gov/24991839/	unhealthy, median age 64 years Health Status: unhealthy Age Group: median age 64 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/	DLT: Nausea, Vomiting... Other AEs: Lymphopenia, Anemia... Dose limiting toxicities: Nausea (grade 3, 13%) Vomiting (grade 3, 13%) Other AEs: Lymphopenia (grade 3-4, 13%) Anemia (grade 1-2, 13%) Thrombocytopenia (grade 1-2, 13%) Anorexia (grade 1-2, 38%) Bradycardia (grade 1-2, 13%) Constipation (grade 1-2, 25%) Diarrhea (grade 1-2, 25%) Fatigue (grade 1-2, 88%) Hypotension (grade 1-2, 13%) Nausea (grade 1-2, 50%) Rash (grade 1-2, 13%) Vomiting (grade 1-2, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/
200 mg 2 times / day multiple, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/	unhealthy, median age 64 years Health Status: unhealthy Age Group: median age 64 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/	DLT: Heart block... Dose limiting toxicities: Heart block (grade 3, 6.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/
500 mg 2 times / day multiple, oral Studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/	unhealthy, median age 64 years Health Status: unhealthy Age Group: median age 64 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/	DLT: Rash... Dose limiting toxicities: Rash (grade 3, 14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/24991839/
200 mg 2 times / day steady, oral Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01537315	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT01537315	Other AEs: Increased blood pressure... Other AEs: Increased blood pressure (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01537315

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C8 810 CYP3A5 446

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 2546	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2015042/	yes		yes (co-administration study) Comment: Concomitant administration of HCQ increased the bioavailability of metoprolol, as indicated by significant increases in the area under the plasma concentration-time curve (65 ± 4.6%) and maximal plasma concentrations (72 ± 6.9%) of metoprolol Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2015042/

Drug as victim

Target	Modality	Activity
CYP2C8 810	substrate 4014 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/art.39402; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600351/	likely
CYP2D6 1388	substrate 4014 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/art.39402; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600351/	likely
CYP3A4 1946	substrate 4014 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/art.39402; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600351/	likely
CYP3A5 446	substrate 4014 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/art.39402; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600351/	likely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/33674391/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5801	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5801
ChemicalBook	CB6866802	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6866802
eMolecules	901965	https://www.emolecules.com/cgi-bin/more?vid=901965
MolPort	MolPort-003-847-792	https://www.molport.com/shop/molecule-link/MolPort-003-847-792

PubMed

Title	Date	PubMed
Antimalarial drugs in systemic lupus erythematosus: use in pregnancy.	2001	11735661
[Amphiphilic cationic drug myopathy, drug-induced lysosomal storage lipidosis].	2001	11596386
Management of hepatitis C virus-related arthritis.	2001	11580301
Antimalarials--the 'real' advance in lupus.	2001	11434570
Treatment of rheumatoid arthritis: unknown long-term effects.	2001 Apr	11718162
Leflunomide and rheumatoid arthritis: new preparation. Neither the safest nor the most effective slow-acting antirheumatic drug.	2001 Apr	11718154
Pilot tolerability studies of hydroxychloroquine and colchicine in Alzheimer disease.	2001 Apr-Jun	11403336
Early hydroxychloroquine macular toxicity.	2001 Aug	11508449
Bromocriptine in rheumatic and autoimmune diseases.	2001 Aug	11503136
Risks factors and prevention of Q fever endocarditis.	2001 Aug 1	11438895
Angiooedema due to acquired deficiency of C1-esterase inhibitor associated with leucocytoclastic vasculitis.	2001 Aug-Sep	11720182
Hydroxychloroquine retinopathy.	2001 Dec	11733247
Fatal toxic epidermal necrolysis associated with hydroxychloroquine.	2001 Jul	11488840
Hydroxychloroquine enhances the endocrine secretion of adenovirus-directed growth hormone from rat submandibular glands in vivo.	2001 Jul 1	11440626
Treating early rheumatoid arthritis in the younger patient.	2001 Jun	11409156
Conventional DMARD options for patients with a suboptimal response to methotrexate.	2001 Jun	11409154
Disease modifying antirheumatic drugs: longterm safety issues.	2001 Jun	11409152
Rheumatologists' attitudes toward routine screening for hydroxychloroquine retinopathy.	2001 Jun	11409112
Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?	2001 Jun	11384574
Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.	2001 Jun 1	11359853
The additive in vitro anti-HIV-1 effect of chloroquine, when combined with zidovudine and hydroxyurea.	2001 Jun 15	11377382
[Lymphedema of the upper limb, a complication of rheumatoid polyarthritis].	2001 Jun 30	11484403
[Photodermatosis induced by hydroxychloroquine: 4 cases].	2001 Jun-Jul	11460035
Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus.	2001 Mar	11495297
Progression of hydroxychloroquine retinopathy after discontinuation of therapy: case report.	2001 May	11480331
Current concepts regarding pharmacologic treatment of rheumatoid and osteoarthritis.	2001 May	11478054
Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.	2001 May	11401667
Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia.	2001 Nov	11708429
Dermatomyositis.	2001 Nov 1	11730311
[Psychiatric manifestations of lupus erythematosus systemic and Sjogren's syndrome].	2001 Nov-Dec	11865567
Modulation of hormones in the treatment of lupus.	2001 Oct	11680780
Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine.	2001 Oct	11665963
Leflunomide for the treatment of systemic lupus erythematosus: comment on the article by McMurray.	2001 Oct	11642648
Dermatomyositis and Graves' disease.	2001 Sep-Oct	11579725
Safety and efficacy of disease-modifying anti-rheumatic agents: focus on the benefits and risks of etanercept.	2002	11945114
Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus.	2002	11898921
Evidence of transplacental passage of hydroxychloroquine in humans.	2002 Apr	11953993
Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.	2002 Apr	11953964
Canadian Consensus Conference on hydroxychloroquine.	2002 Apr	11950041
Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis.	2002 Apr	11950006
Pharmacoeconomics of long-term treatment of rheumatoid arthritis.	2002 Apr	11934345
[Primary Gougerot-Sjögren syndrome in a 13-year-old girl].	2002 Feb	11915495
How frequently and how soon should we screen our patients for the presence of antimalarial retinopathy?	2002 Feb	11840465
Antimalarial agents in pregnancy.	2002 Feb 9	11853823
Second-line drugs used in recent-onset rheumatoid arthritis in Brittany (France).	2002 Jan	11858354
Chloroquine decreases cell-surface expression of tumour necrosis factor receptors in human histiocytic U-937 cells.	2002 Jan	11849318
IgM antibodies against cytomegalovirus in SLE nephritis: viral infection or aspecific autoantibody?	2002 Jan-Feb	11936434
Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies.	2002 Mar	11916085
Nonendemic pemphigus foliaceus in children.	2002 Mar	11862179
The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial.	2002 Mar	11850097

Patents

Sample Use Guides

In Vivo Use Guide

Malaria: Suppression— In adults, 400 mg (=310 mg base) on exactly the same day of each week. In infants and children, the weekly suppressive dosage is 5 mg, calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

Route of Administration: Oral

In Vitro Use Guide

After 48 hours of stimulation with PMA and ionomycin, Hydroxychloroquine (25-100 uM) inhibited the production of IL-6, IL-17 and IL-22 in the PBMCs of healthy volunteers

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:45:27 GMT 2025` Edited by `admin` on `Wed Apr 02 09:45:27 GMT 2025`
Record UNII	4QWG6N8QKH
Record Status	`Validated (UNII)`
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Name

Type

Language

HYDROXYCHLOROQUINE

Official Name

English

POLIRREUMIN

Preferred Name

English

hydroxychloroquine [INN]

Common Name

English

HYDROXYCHLOROQUINE [MI]

Common Name

English

(±)-2-((4-((7-CHLORO-4-QUINOLYL)AMINO)PENTYL)ETHYLAMINO)ETHANOL

Systematic Name

English

HYDROXYCHLOROQUINE [VANDF]

Common Name

English

Hydroxychloroquine [WHO-DD]

Common Name

English

ETHANOL, 2-((4-((7-CHLORO-4-QUINOLINYL)AMINO)PENTYL)ETHYL)AMINO-, (±)-

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/16/1820