Identification
NameNiclosamide
Accession NumberDB06803
TypeSmall Molecule
GroupsApproved, Vet Approved
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
Niclocide
External IDs BAY 2353 / NSC-178296 / WR 46234
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
NiclocideNot Available
Brand mixturesNot Available
Categories
UNII8KK8CQ2K8G
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
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.

Structured Indications Not Available
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
DNANucleotideunknown
antagonist
Humannot applicabledetails
Related Articles
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 distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity

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

Affected organisms
  • Helminthic Microorganisms
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Niclosamide can be decreased when combined with Abiraterone.Approved
AmiodaroneThe metabolism of Niclosamide can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Niclosamide can be decreased when it is combined with Amodiaquine.Approved
AprepitantThe metabolism of Niclosamide can be increased when combined with Aprepitant.Approved, Investigational
CapecitabineThe metabolism of Niclosamide can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Niclosamide can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Niclosamide can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Niclosamide can be decreased when it is combined with Chloroquine.Approved, Vet Approved
CholecalciferolThe metabolism of Niclosamide can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
ClotrimazoleThe metabolism of Niclosamide can be decreased when combined with Clotrimazole.Approved, Vet Approved
CyclosporineThe metabolism of Niclosamide can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Niclosamide can be decreased when it is combined with Dabrafenib.Approved
DelavirdineThe metabolism of Niclosamide can be decreased when combined with Delavirdine.Approved
EfavirenzThe metabolism of Niclosamide can be decreased when combined with Efavirenz.Approved, Investigational
EtravirineThe metabolism of Niclosamide can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Niclosamide can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Niclosamide can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Niclosamide can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Niclosamide can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Niclosamide can be decreased when combined with Fluvoxamine.Approved, Investigational
FosphenytoinThe metabolism of Niclosamide can be increased when combined with Fosphenytoin.Approved
GemfibrozilThe metabolism of Niclosamide can be decreased when combined with Gemfibrozil.Approved
HydroxychloroquineThe serum concentration of Niclosamide can be decreased when it is combined with Hydroxychloroquine.Approved
IndinavirThe metabolism of Niclosamide can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Niclosamide can be decreased when combined with Irbesartan.Approved, Investigational
KetoconazoleThe metabolism of Niclosamide can be decreased when combined with Ketoconazole.Approved, Investigational
LeflunomideThe metabolism of Niclosamide can be decreased when combined with Leflunomide.Approved, Investigational
LosartanThe metabolism of Niclosamide can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Niclosamide can be decreased when combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Niclosamide can be decreased when it is combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Niclosamide can be increased when it is combined with Mifepristone.Approved, Investigational
NicardipineThe metabolism of Niclosamide can be decreased when combined with Nicardipine.Approved
OmeprazoleThe metabolism of Niclosamide can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Niclosamide can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Niclosamide can be increased when combined with Phenytoin.Approved, Vet Approved
PrimaquineThe serum concentration of Niclosamide can be decreased when it is combined with Primaquine.Approved
PrimidoneThe metabolism of Niclosamide can be increased when combined with Primidone.Approved, Vet Approved
PyrimethamineThe metabolism of Niclosamide can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinineThe metabolism of Niclosamide can be decreased when combined with Quinine.Approved
RifampicinThe metabolism of Niclosamide can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Niclosamide can be increased when combined with Rifapentine.Approved
SecobarbitalThe metabolism of Niclosamide can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Niclosamide can be decreased when combined with Sildenafil.Approved, Investigational
SorafenibThe metabolism of Niclosamide can be decreased when combined with Sorafenib.Approved, Investigational
SulfadiazineThe metabolism of Niclosamide can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Niclosamide can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Niclosamide can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TicagrelorThe metabolism of Niclosamide can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Niclosamide can be decreased when combined with Ticlopidine.Approved
TolbutamideThe metabolism of Niclosamide can be decreased when combined with Tolbutamide.Approved
TrimethoprimThe metabolism of Niclosamide can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Niclosamide can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Niclosamide can be decreased when combined with Valsartan.Approved, Investigational
VoriconazoleThe metabolism of Niclosamide can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Niclosamide can be decreased when combined with Zafirlukast.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceUS3079297
General References
  1. Thomson Micromedex (2007). Advice for the Patient Volume II (27th ed.). PDR Network, LLC. [ISBN:1-56363-575-5 ]
External Links
ATC CodesP02DA01 — Niclosamide
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Cancer1
1RecruitingOtherMalignant Neoplasm of Colon1
1RecruitingTreatmentCastration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / Hormone-Resistant Prostate Cancer / Metastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Adenocarcinoma1
1, 2RecruitingOtherRheumatoid Arthritis1
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Cancer1
Not AvailableCompletedScreeningTaenia Solium Taeniasis1
Not AvailableTerminatedTreatmentIntestinal Parasitism1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0029000000-07d09d3c05d206cf1709View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00dr-0982000000-be44b0c8755c752ba0f3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0910000000-4aa0326731fc70d171deView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0900000000-d166a8246615e944705aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0900000000-8da8fb85b28f330b445dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0abi-0900000000-10c251c2f1c5006a7f25View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0fka-5952000000-25e2c37ca8eb59d1db22View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-9200000000-57c28b8b2b3dc926256dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-9100000000-2b567071c6cfa78ecf55View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-9100000000-33d3827b1d5b1d8b0dd1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-9000000000-9cee7be3f0ec47a2cf6eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-9000000000-cf3d1288bd0150e477beView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-0519000000-8dd141b868e2002a2bfaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udi-4900000000-d83bc5ee9b78c460078cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentBenzanilides
Alternative ParentsSalicylamides / 3-halobenzoic acids and derivatives / Benzamides / Nitrobenzenes / P-chlorophenols / Benzoyl derivatives / Nitroaromatic compounds / 1-hydroxy-2-unsubstituted benzenoids / Chlorobenzenes / Aryl chlorides
SubstituentsBenzanilide / Salicylamide / Salicylic acid or derivatives / 3-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzamide / Benzoic acid or derivatives / Nitrobenzene / Nitroaromatic compound / Benzoyl
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
unknown
Actions
antagonist
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. 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
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
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 June 24, 2017 13:27