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Identification
Name Hydroxychloroquine
Accession Number DB01611
Type small molecule
Groups approved
Description

A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
HCQ
Salts
  • Hydroxychloroquine sulfate
Brand names
Name Company
Axemal
Dolquine
Ercoquin
Plaquenil
Polirreumin
Quensyl
Brand mixtures Not Available
Categories
  • Antirheumatic Agents
  • Enzyme Inhibitors
  • Antimalarials
  • Dermatologic Agents
  • Antiprotozoal Agents
CAS number 118-42-3
Weight Average: 335.872
Monoisotopic: 335.176440176
Chemical Formula C18H26ClN3O
InChI Key InChIKey=XXSMGPRMXLTPCZ-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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminoquinolines and Derivatives
  • (Iso)quinolines and Derivatives
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Benzene and Derivatives
  • Aryl Halides
  • Aminoquinolines and Derivatives
  • Halobenzenes
  • Aminopyridines and Derivatives
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
Pharmacology
Indication 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.
Pharmacodynamics Hydroxychloroquine 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 action 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.
Absorption Very rapidly and completely absorbed following oral administration.
Volume of distribution Not Available
Protein binding Approximately 45%.
Metabolism
Partially hepatic, to active de-ethylated metabolites.
Route of elimination Not Available
Half life Terminal elimination half-life In blood is approximately 50 days. In plasma it is approximately 32 days.
Clearance Not Available
Toxicity Symptoms 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
Pathways Not Available
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
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Hydroxychloroquine sulf powder 4.8 USD g
Plaquenil 200 mg tablet 3.14 USD tablet
Hydroxychloroquine Sulfate 200 mg tablet 1.28 USD tablet
Hydroxychloroquine 200 mg tablet 1.17 USD tablet
Plaquenil Sulfate 200 mg Tablet 0.66 USD tablet
Apo-Hydroxyquine 200 mg Tablet 0.35 USD tablet
Mylan-Hydroxychloroquine 200 mg Tablet 0.35 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 90 °C PhysProp
Predicted Properties
Property Value Source
water solubility 2.61e-02 g/l ALOGPS
logP 3.87 ALOGPS
logP 2.89 ChemAxon
logS -4.1 ALOGPS
pKa (strongest acidic) 15.59 ChemAxon
pKa (strongest basic) 9.76 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 48.39 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 97.97 ChemAxon
polarizability 38.3 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D08050 Link_out
KEGG Compound C07043 Link_out
PubChem Compound 3652 Link_out
PubChem Substance 46508459 Link_out
ChemSpider 3526 Link_out
Therapeutic Targets Database DAP000878 Link_out
PharmGKB PA164777036 Link_out
Drug Product Database 2017709 Link_out
RxList http://www.rxlist.com/cgi/generic/hquine.htm Link_out
Drugs.com http://www.drugs.com/cdi/hydroxychloroquine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Hydroxychloroquine Link_out
ATC Codes
  • P01BA02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Artemether Hydroxychloroquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Digoxin Hydroxychloroquine increases the effect of digoxin
Lumefantrine Hydroxychloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
Methotrexate Hydroxychloroquine increases the effect and toxicity of methotrexate
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

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

Pharmacological action: yes
Actions: antagonist

Participates in the innate immune response to microbial agents. Acts via MyD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response

Organism class: human
UniProt ID: Q9NYK1 Link_out
Gene: TLR7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

Participates in the innate immune response to microbial agents. Detects the unmethylated cytidine-phosphate-guanosine (CpG) motifs present in bacterial DNA. Acts via MyD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response

Organism class: human
UniProt ID: Q9NR96 Link_out
Gene: TLR9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on August 29, 2007 14:00 / Updated on February 08, 2013 16:20