Identification

Name
Niclosamide
Accession Number
DB06803
Description

Niclosamide is an antihelminthic used for the treatment of 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.

Niclosamide, once marketed in the US under the brand name Niclocide, was voluntarily withdrawn from market by Bayer in 1996.2

Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Structure
Thumb
Weight
Average: 327.12
Monoisotopic: 325.986112168
Chemical Formula
C13H8Cl2N2O4
Synonyms
Not Available
External IDs
  • BAY 2353
  • NSC-178296
  • WR 46234

Pharmacology

Indication

For 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.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Niclosamide 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 action

Niclosamide 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.

TargetActionsOrganism
UDNA
antagonist
Humans
Absorption

Niclosamide 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 distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Infrequent, mild, and transitory adverse events include nausea, vomiting, diarrhea, and abdominal discomfort.

Affected organisms
  • Helminthic Microorganisms
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe metabolism of Niclosamide can be increased when combined with Abatacept.
AbirateroneThe metabolism of Niclosamide can be decreased when combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Niclosamide.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Niclosamide.
AcetohexamideThe metabolism of Niclosamide can be decreased when combined with Acetohexamide.
Acetyl sulfisoxazoleThe metabolism of Niclosamide can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe metabolism of Niclosamide can be decreased when combined with Acetylsalicylic acid.
AcyclovirThe metabolism of Acyclovir can be decreased when combined with Niclosamide.
AdalimumabThe metabolism of Niclosamide can be increased when combined with Adalimumab.
AgomelatineThe metabolism of Agomelatine can be decreased when combined with Niclosamide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

International/Other Brands
Niclocide

Categories

ATC Codes
P02DA01 — Niclosamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Salicylamides / 3-halobenzoic acids and derivatives / Benzamides / Nitrobenzenes / P-chlorophenols / Benzoyl derivatives / Nitroaromatic compounds / 1-hydroxy-2-unsubstituted benzenoids / Chlorobenzenes / Aryl chlorides
show 11 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / 3-halobenzoic acid or derivatives / 4-chlorophenol / 4-halophenol / Allyl-type 1,3-dipolar organic compound / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzamide / Benzanilide
show 29 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
8KK8CQ2K8G
CAS number
50-65-7
InChI Key
RJMUSRYZPJIFPJ-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

References

Synthesis Reference
US3079297
General References
  1. Thomson Micromedex (2007). Advice for the Patient Volume II (27th ed.). PDR Network, LLC. [ISBN:1-56363-575-5]
  2. Federal Register: Withdrawal of Approval of 29 NADA's (July 3, 1996) [Link]
Human Metabolome Database
HMDB0015679
KEGG Drug
D00436
PubChem Compound
4477
PubChem Substance
99443295
ChemSpider
4322
BindingDB
11242
RxNav
7402
ChEBI
7553
ChEMBL
CHEMBL1448
ZINC
ZINC000003874496
PharmGKB
PA165958408
Drugs.com
Drugs.com Drug Page
Wikipedia
Niclosamide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingTreatmentNephropathy, Diabetic1
3Not Yet RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)1
2Not Yet RecruitingTreatmentCOVID / COVID - 19 / Novel Coronavirus Infectious Disease (COVID-19)1
2Not Yet RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)2
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentFamilial Adenomatous Polyposis (FAP)1
2RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Cancer1
1CompletedTreatmentCastration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / Hormone-Resistant Prostate Cancer / Metastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Adenocarcinoma1
1RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Cancer1
1TerminatedOtherMalignant Neoplasm of Colon1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet500 mg
TabletOral500 MG
Tablet0.5 g
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)230 °CPhysProp
water solubility1.6 mg/L (at 20 °C)TOMLIN,C (1997)
Predicted Properties
PropertyValueSource
Water Solubility0.00799 mg/mLALOGPS
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 Area95.15 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity80.51 m3·mol-1ChemAxon
Polarizability28.47 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7721
Blood Brain Barrier+0.7259
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.7857
P-glycoprotein inhibitor INon-inhibitor0.8671
P-glycoprotein inhibitor IINon-inhibitor0.9349
Renal organic cation transporterNon-inhibitor0.9267
CYP450 2C9 substrateNon-substrate0.721
CYP450 2D6 substrateNon-substrate0.8519
CYP450 3A4 substrateSubstrate0.5187
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.6943
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8442
Ames testAMES toxic0.9107
CarcinogenicityCarcinogens 0.5513
BiodegradationNot ready biodegradable0.9803
Rat acute toxicity2.2390 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.914
hERG inhibition (predictor II)Non-inhibitor0.8434
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0029000000-07d09d3c05d206cf1709
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00dr-0982000000-be44b0c8755c752ba0f3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0910000000-4aa0326731fc70d171de
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-d166a8246615e944705a
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-8da8fb85b28f330b445d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0abi-0900000000-10c251c2f1c5006a7f25
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0fka-5952000000-25e2c37ca8eb59d1db22
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9200000000-57c28b8b2b3dc926256d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9100000000-2b567071c6cfa78ecf55
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9100000000-33d3827b1d5b1d8b0dd1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9000000000-9cee7be3f0ec47a2cf6e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9000000000-cf3d1288bd0150e477be
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0519000000-8dd141b868e2002a2bfa
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-4900000000-d83bc5ee9b78c460078c

Targets

Kind
Nucleotide
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
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.
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:12392939]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
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:11124226]
  2. Egnell AC, Eriksson C, Albertson N, Houston B, Boyer S: Generation and evaluation of a CYP2C9 heteroactivation pharmacophore. J Pharmacol Exp Ther. 2003 Dec;307(3):878-87. Epub 2003 Oct 13. [PubMed:14557374]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data limited to in vitro studies.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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:11124226]

Drug created on September 14, 2010 10:21 / Updated on August 01, 2020 06:24

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