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Identification
NameNiclosamide
Accession NumberDB06803
Typesmall molecule
Groupsapproved
Description

Niclosamide is used for the treatment of most tapeworm infections. Helminths (worms) are multicellular organisms that infect very large numbers of humans and cause a broad range of diseases. Over 1 billion people are infected with intestinal nematodes, and many millions are infected with filarial nematodes, flukes, and tapeworms. They are an even greater problem in domestic animals.

Structure
Thumb
Synonyms
SynonymLanguageCode
NiclocideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
NiclocideNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number50-65-7
WeightAverage: 327.12
Monoisotopic: 325.986112168
Chemical FormulaC13H8Cl2N2O4
InChI KeyRJMUSRYZPJIFPJ-UHFFFAOYSA-N
InChI
InChI=1S/C13H8Cl2N2O4/c14-7-1-4-12(18)9(5-7)13(19)16-11-3-2-8(17(20)21)6-10(11)15/h1-6,18H,(H,16,19)
IUPAC Name
5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide
SMILES
OC1=C(C=C(Cl)C=C1)C(=O)NC1=C(Cl)C=C(C=C1)[N+]([O-])=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentN-phenylbenzamides
Alternative parentsAnilides; Salicylamides; Nitrobenzenes; p-Chlorophenols; Benzoyl Derivatives; Chlorobenzenes; Aryl Chlorides; Secondary Carboxylic Acid Amides; Nitro Compounds; Nitronic Acids; Enols; Enolates; Carboxylic Acids; Polyamines; Organic Oxoazanium Compounds; Organochlorides
Substituentsacetanilide; salicylamide; salicylic acid or derivative; nitrobenzene; 4-chlorophenol; 4-halophenol; benzoyl; phenol derivative; chlorobenzene; aryl chloride; aryl halide; nitro compound; secondary carboxylic acid amide; carboxamide group; nitronic acid; enolate; polyamine; enol; carboxylic acid derivative; carboxylic acid; organic oxoazanium; organohalogen; organochloride; amine; organonitrogen compound
Classification descriptionThis compound belongs to the n-phenylbenzamides.
Pharmacology
IndicationFor the treatment of tapeworm and intestinal fluke infections: Taenia saginata (Beef Tapeworm), Taenia solium (Pork Tapeworm), Diphyllobothrium latum (Fish Tapeworm), Fasciolopsis buski (large intestinal fluke). Niclosamide is also used as a molluscicide in the control of schistosomiasis.
PharmacodynamicsNiclosamide is an antihelminth used against tapeworm infections. It may act by the uncoupling of the electron transport chain to ATP synthase. The disturbance of this crucial metabolic pathway prevents creation of adenosine tri-phosphate (ATP), an essential molecule that supplies energy for metabolism.
Mechanism of actionNiclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity. The killed worms are then passed in the stool or sometimes destroyed in the intestine. Niclosamide may work as a molluscicide by binding to and damaging DNA.
AbsorptionNiclosamide appears to be minimally absorbed from the gastrointestinal tract—neither the drug nor its metabolites have been recovered from the blood or urine.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityInfrequent, mild, and transitory adverse events include nausea, vomiting, diarrhea, and abdominal discomfort.
Affected organisms
  • Helminthic Microorganisms
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7721
Blood Brain Barrier + 0.7259
Caco-2 permeable + 0.5
P-glycoprotein substrate Non-substrate 0.7857
P-glycoprotein inhibitor I Non-inhibitor 0.8671
P-glycoprotein inhibitor II Non-inhibitor 0.9349
Renal organic cation transporter Non-inhibitor 0.9267
CYP450 2C9 substrate Non-substrate 0.721
CYP450 2D6 substrate Non-substrate 0.8519
CYP450 3A4 substrate Substrate 0.5187
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.8948
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Inhibitor 0.6943
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8442
Ames test AMES toxic 0.9107
Carcinogenicity Carcinogens 0.5513
Biodegradation Not ready biodegradable 0.9803
Rat acute toxicity 2.2390 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.914
hERG inhibition (predictor II) Non-inhibitor 0.8434
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, chewableOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point230 °CPhysProp
water solubility1.6 mg/L (at 20 °C)TOMLIN,C (1997)
Predicted Properties
PropertyValueSource
water solubility7.99e-03 g/lALOGPS
logP4.49ALOGPS
logP3.91ChemAxon
logS-4.6ALOGPS
pKa (strongest acidic)6.89ChemAxon
pKa (strongest basic)-4.4ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area95.15ChemAxon
rotatable bond count3ChemAxon
refractivity80.51ChemAxon
polarizability28.47ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3079297
General Reference
  1. Rosenthal Philip J, “Chapter 53. Clinical Pharmacology of the Antihelminthic Drugs” (Chapter). Katzung BG: Basic & Clinical Pharmacology, 11e: http://www.accessmedicine.com/content.aspx?aID=4516635.
  2. 2010. Detailed Drug Information for the Consumer™. Greenwood Village, CO. Thomson Reuters. ISBN-10: 1-56363-575-5. ISSN: 0740-4174. STAT!Ref Online Electronic Medical Library.
External Links
ResourceLink
KEGG DrugD00436
PubChem Compound4477
PubChem Substance99443295
ChemSpider4322
PharmGKBPA165958408
Drugs.comhttp://www.drugs.com/cons/niclosamide.html
WikipediaNiclosamide
ATC CodesP02DA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details

References:

  1. Abreu FC, Goulart MO, Brett AM: Detection of the damage caused to DNA by niclosamide using an electrochemical DNA-biosensor. Biosens Bioelectron. 2002 Dec;17(11-12):913-9. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Bapiro TE, Egnell AC, Hasler JA, Masimirembwa CM: Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Bapiro TE, Egnell AC, Hasler JA, Masimirembwa CM: Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5. Pubmed

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Drug created on September 14, 2010 10:21 / Updated on October 08, 2013 14:24