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Identification
NameHydroxychloroquine
Accession NumberDB01611
Typesmall molecule
Groupsapproved
Description

A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites.

Structure
Thumb
Synonyms
SynonymLanguageCode
(+-)-HydroxychloroquineNot AvailableNot Available
(±)-hydroxychloroquineNot AvailableNot Available
2-((4-((7-chloro-4-Quinolyl)amino)pentyl)ethylamino)ethanolNot AvailableNot Available
2-(N-(4-(7-Chlor-4-chinolylamino)-4-methylbutyl)ethylamino)ethanolNot AvailableNot Available
7-chloro-4-(4-(Ethyl(2-hydroxyethyl)amino)-1-methylbutylamino)quinolineNot AvailableNot Available
7-chloro-4-(4-(N-Ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino)quinolineNot AvailableNot Available
7-chloro-4-[4-(N-Ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino]quinolineNot AvailableNot Available
7-chloro-4-[5-(N-Ethyl-N-2-hydroxyethylamino)-2-pentyl]aminoquinolineNot AvailableNot Available
HidroxicloroquinaNot AvailableNot Available
HydroxychloroquinumNot AvailableNot Available
NSC4375Not AvailableNot Available
OxichlorochineNot AvailableNot Available
OxichloroquineNot AvailableNot Available
PolirreuminNot AvailableNot Available
Salts
Name/CAS Structure Properties
Hydroxychloroquine sulfate
Thumb
  • InChI Key: JCBIVZZPXRZKTI-UHFFFAOYNA-N
  • Monoisotopic Mass: 433.143819418
  • Average Mass: 433.95
DBSALT000096
Brand names
NameCompany
AxokineAstraZeneca
DolquineInmunosyn
HCQSMedigroup
PlaquenilSanofi
PolirreuminTRB
QuensylSanofi
Brand mixturesNot Available
Categories
CAS number118-42-3
WeightAverage: 335.872
Monoisotopic: 335.176440176
Chemical FormulaC18H26ClN3O
InChI KeyXXSMGPRMXLTPCZ-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-({4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino)ethan-1-ol
SMILES
CCN(CCO)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassAminoquinolines and Derivatives
Direct parentAminoquinolines and Derivatives
Alternative parentsAminopyridines and Derivatives; Chlorobenzenes; Aryl Chlorides; Tertiary Amines; Polyamines; Secondary Amines; Primary Alcohols; Organochlorides
Substituentsaminopyridine; chlorobenzene; aryl halide; pyridine; benzene; aryl chloride; tertiary amine; primary alcohol; polyamine; secondary amine; amine; organohalogen; organochloride; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the aminoquinolines and derivatives. These are organic compounds containing an amino group attached to a quinoline ring system.
Pharmacology
IndicationFor 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.
PharmacodynamicsHydroxychloroquine possesses antimalarial properties and also exerts a beneficial effect in lupus erythematosus (chronic discoid or systemic) and acute or chronic rheumatoid arthritis. The precise mechanism of action is not known.
Mechanism of actionAlthough 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.
AbsorptionVery rapidly and completely absorbed following oral administration.
Volume of distributionNot Available
Protein bindingApproximately 45%.
Metabolism

Partially hepatic, to active de-ethylated metabolites.

Route of eliminationNot Available
Half lifeTerminal elimination half-life In blood is approximately 50 days. In plasma it is approximately 32 days.
ClearanceNot Available
ToxicitySymptoms of overdose include headache, drowsiness, visual disturbances, cardiovascular collapse, and convulsions, followed by sudden and early respiratory and cardiac arrest. The electrocardiogram may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, and progressive bradycardia leading to ventricular fibrillation and/or arrest.
Affected organisms
  • Plasmodium
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9892
Blood Brain Barrier + 0.5602
Caco-2 permeable - 0.5154
P-glycoprotein substrate Substrate 0.8348
P-glycoprotein inhibitor I Non-inhibitor 0.7297
P-glycoprotein inhibitor II Inhibitor 0.5106
Renal organic cation transporter Non-inhibitor 0.5742
CYP450 2C9 substrate Non-substrate 0.8239
CYP450 2D6 substrate Non-substrate 0.9117
CYP450 3A4 substrate Non-substrate 0.5384
CYP450 1A2 substrate Non-inhibitor 0.5864
CYP450 2C9 substrate Non-inhibitor 0.8457
CYP450 2D6 substrate Non-inhibitor 0.6111
CYP450 2C19 substrate Non-inhibitor 0.8782
CYP450 3A4 substrate Non-inhibitor 0.6287
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7058
Ames test AMES toxic 0.6907
Carcinogenicity Non-carcinogens 0.837
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.6348 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6798
hERG inhibition (predictor II) Inhibitor 0.7173
Pharmacoeconomics
Manufacturers
  • Ipca laboratories ltd
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Zydus pharmaceuticals usa inc
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Hydroxychloroquine sulf powder4.8USDg
Plaquenil 200 mg tablet3.14USDtablet
Hydroxychloroquine Sulfate 200 mg tablet1.28USDtablet
Hydroxychloroquine 200 mg tablet1.17USDtablet
Plaquenil Sulfate 200 mg Tablet0.66USDtablet
Apo-Hydroxyquine 200 mg Tablet0.35USDtablet
Mylan-Hydroxychloroquine 200 mg Tablet0.35USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point89-91U.S. Patent 2,546,658.
Predicted Properties
PropertyValueSource
water solubility2.61e-02 g/lALOGPS
logP3.87ALOGPS
logP2.89ChemAxon
logS-4.1ALOGPS
pKa (strongest acidic)15.59ChemAxon
pKa (strongest basic)9.76ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area48.39ChemAxon
rotatable bond count9ChemAxon
refractivity97.97ChemAxon
polarizability38.3ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 2,546,658.

General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD08050
KEGG CompoundC07043
PubChem Compound3652
PubChem Substance46508459
ChemSpider3526
Therapeutic Targets DatabaseDAP000878
PharmGKBPA164777036
Drug Product Database2017709
RxListhttp://www.rxlist.com/cgi/generic/hquine.htm
Drugs.comhttp://www.drugs.com/cdi/hydroxychloroquine.html
WikipediaHydroxychloroquine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
ArtemetherHydroxychloroquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
DigoxinHydroxychloroquine increases the effect of digoxin
LumefantrineHydroxychloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
MethotrexateHydroxychloroquine increases the effect and toxicity of methotrexate
Rilonaceptresults in increased immunosuppressive effects; increases the risk of infection.
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: cross-linking/alkylation

Components

Name UniProt ID Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Koranda FC: Antimalarials. J Am Acad Dermatol. 1981 Jun;4(6):650-5. Pubmed

2. Toll-like receptor 7

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Toll-like receptor 7 Q9NYK1 Details

References:

  1. Sun S, Rao NL, Venable J, Thurmond R, Karlsson L: TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35. Pubmed
  2. Trevani AS, Chorny A, Salamone G, Vermeulen M, Gamberale R, Schettini J, Raiden S, Geffner J: Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur J Immunol. 2003 Nov;33(11):3164-74. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Toll-like receptor 9

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Toll-like receptor 9 Q9NR96 Details

References:

  1. Sun S, Rao NL, Venable J, Thurmond R, Karlsson L: TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35. Pubmed
  2. Trevani AS, Chorny A, Salamone G, Vermeulen M, Gamberale R, Schettini J, Raiden S, Geffner J: Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur J Immunol. 2003 Nov;33(11):3164-74. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M: Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br J Clin Pharmacol. 2000 Jun;49(6):549-54. Pubmed

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Drug created on August 29, 2007 14:00 / Updated on April 29, 2014 11:05