Identification

Name
Niclosamide
Accession Number
DB06803
Type
Small Molecule
Groups
Approved, Investigational, 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
Not Available
External IDs
BAY 2353 / NSC-178296 / WR 46234
International/Other Brands
Niclocide
Categories
UNII
8KK8CQ2K8G
CAS number
50-65-7
Weight
Average: 327.12
Monoisotopic: 325.986112168
Chemical Formula
C13H8Cl2N2O4
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

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.

TargetActionsOrganism
UDNA
antagonist
Human
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
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
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, Investigational
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
CrisaboroleThe metabolism of Niclosamide can be decreased when combined with Crisaborole.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
DosulepinThe metabolism of Niclosamide can be decreased when combined with Dosulepin.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
LobeglitazoneThe metabolism of Niclosamide can be decreased when combined with Lobeglitazone.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
ManidipineThe metabolism of Niclosamide can be decreased when combined with Manidipine.Approved, Investigational
MidostaurinThe metabolism of Niclosamide can be decreased when combined with Midostaurin.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
TopiroxostatThe metabolism of Niclosamide can be decreased when combined with Topiroxostat.Approved, Investigational
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 Interactions
Not Available

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]
External Links
Human Metabolome Database
HMDB15679
KEGG Drug
D00436
PubChem Compound
4477
PubChem Substance
99443295
ChemSpider
4322
BindingDB
11242
ChEBI
7553
ChEMBL
CHEMBL1448
PharmGKB
PA165958408
Drugs.com
Drugs.com Drug Page
Wikipedia
Niclosamide
ATC Codes
P02DA01 — Niclosamide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
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
1RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer / Recurrent Prostate Carcinoma / Stage IV Prostate Cancer1
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

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
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

Taxonomy

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
Benzanilide / Salicylamide / Salicylic acid or derivatives / 3-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzamide / Benzoic acid or derivatives / Nitrobenzene / Nitroaromatic compound / Benzoyl
show 29 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not 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 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]
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 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 November 09, 2017 03:56