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Record Information
Version2.0
Creation Date2009-07-30 17:58:56 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3512
Identification
Common NameHydroxychloroquine
ClassSmall Molecule
DescriptionHydroxychloroquine is only found in individuals that have used or taken this drug. It is a chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. 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.
Compound Type
  • Amine
  • Antimalarial
  • Antirheumatic Agent
  • Dermatologic Agent
  • Drug
  • Enzyme Inhibitor
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+-)-Hydroxychloroquine
(±)-hydroxychloroquine
2-((4-((7-chloro-4-Quinolyl)amino)pentyl)ethylamino)ethanol
2-(N-(4-(7-Chlor-4-chinolylamino)-4-methylbutyl)ethylamino)ethanol
7-chloro-4-(4-(Ethyl(2-hydroxyethyl)amino)-1-methylbutylamino)quinoline
7-chloro-4-(4-(N-Ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino)quinoline
7-chloro-4-[4-(N-Ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino]quinoline
7-chloro-4-[5-(N-Ethyl-N-2-hydroxyethylamino)-2-pentyl]aminoquinoline
Axokine
Dolquine
HCQ
HCQS
Hidroxicloroquina
Hydroxychloroquinum
NSC4375
Oxichlorochine
Oxichloroquine
Plaquenil
Polirreumin
Quensyl
Chemical FormulaC18H26ClN3O
Average Molecular Mass335.872 g/mol
Monoisotopic Mass335.176 g/mol
CAS Registry Number118-42-3
IUPAC Name2-({4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino)ethan-1-ol
Traditional Namehydroxychloroquine
SMILESCCN(CCO)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1
InChI IdentifierInChI=1/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)
InChI KeyInChIKey=XXSMGPRMXLTPCZ-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassAminoquinolines and derivatives
Direct Parent4-aminoquinolines
Alternative Parents
Substituents
  • Chloroquinoline
  • 4-aminoquinoline
  • Haloquinoline
  • Aminopyridine
  • Secondary aliphatic/aromatic amine
  • Aryl chloride
  • Aryl halide
  • Pyridine
  • Benzenoid
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • 1,2-aminoalcohol
  • Secondary amine
  • Azacycle
  • Alkanolamine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Alcohol
  • Primary alcohol
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point89-91°C
Boiling PointNot Available
Solubility2.61e-02 g/L
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.026 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 Area48.39 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity97.97 m³·mol⁻¹ChemAxon
Polarizability38.3 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05fr-9262000000-58dde1657b5d6098be9bJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00b9-9266000000-ea4f93631dd2ecfd327cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-3ad87c8e6d06353b69a1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-069a-3849000000-89ef84bf56d7c636c87aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-054n-9460000000-09312fdaefa09ffd4066JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-7d2e379f85931a4c8042JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-1229000000-f952822a37d6efa233afJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9641000000-8b6d466c2c58b3345281JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0f6t-3972000000-7c193125680c0c9e276fJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureVery rapidly and completely absorbed following oral administration.
Mechanism of ToxicityAlthough 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.
MetabolismPartially hepatic, to active de-ethylated metabolites. Half Life: Terminal elimination half-life In blood is approximately 50 days. In plasma it is approximately 32 days.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms 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.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01611
HMDB IDHMDB15549
PubChem Compound ID3652
ChEMBL IDCHEMBL1535
ChemSpider ID3526
KEGG IDC07043
UniProt IDNot Available
OMIM ID
ChEBI ID529737
BioCyc IDNot Available
CTD IDNot Available
Stitch IDHydroxychloroquine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkHydroxychloroquine
References
Synthesis Reference

U.S. Patent 2,546,658.

MSDST3D3512.pdf
General ReferencesNot Available
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. [17139284 ]
  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. [17016423 ]
  3. Koranda FC: Antimalarials. J Am Acad Dermatol. 1981 Jun;4(6):650-5. [6165744 ]
General Function:
Transmembrane signaling receptor activity
Specific Function:
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR7 is a nucleotide-sensing TLR which is activated by single-stranded RNA. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity).
Gene Name:
TLR7
Uniprot ID:
Q9NYK1
Molecular Weight:
120920.8 Da
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. [18220957 ]
  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. [14579285 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Transmembrane signaling receptor activity
Specific Function:
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Controls lymphocyte response to Helicobacter infection.
Gene Name:
TLR9
Uniprot ID:
Q9NR96
Molecular Weight:
115858.665 Da
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. [18220957 ]
  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. [14579285 ]