Niclosamide

Identification

Summary

Niclosamide is an anthelmintic indicated in the treatment of beef, pork, fish, and dwarf tapeworm infections in adults and children.

Generic Name
Niclosamide
DrugBank Accession Number
DB06803
Background

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Niclosamide, once marketed in the US under the brand name Niclocide, was voluntarily withdrawn from market by Bayer in 1996.2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
Weight
Average: 327.12
Monoisotopic: 325.986112168
Chemical Formula
C13H8Cl2N2O4
Synonyms
  • Niclosamide
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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatHelminthic infectionCombination Product in combination with: Phenolphthalein (DB04824)••••••••••••••••••
Used in combination to treatTapeworm infestationCombination Product in combination with: Magnesium sulfate (DB00653)••••••••••••••••••
Treatment ofTapeworm infestation••••••••••••••••••
Contraindications & Blackbox Warnings
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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
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Toxicity

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

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.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Niclosamide.
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.
Food Interactions
Not Available

Products

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International/Other Brands
Niclocide
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ยาถ่ายพยาธิตัวตืด ฟ็อบ-เวอร์มินNiclosamide (500 mg) + Phenolphthalein (50 mg)Tabletห้างหุ้นส่วนจำกัด พัฒนาการเภสัช1984-12-132020-09-29Thailand flag
ยาถ่ายพยาธิตัวตืด ฮีโร่ - แอนสันNiclosamide (500 mg) + Phenolphthalein (120 mg)Tabletบริษัท ฮีโร่มัยซิน ฟาร์ม่า จำกัด จำกัด2003-04-20Not applicableThailand flag
ยาถ่ายพยาธิตัวตืดเฮ้กซินNiclosamide (500 mg) + Phenolphthalein (75 mg)Tabletห้างหุ้นส่วนจำกัด ห้างขายยา กรุงเทพฯฟามาซี1985-02-07Not applicableThailand flag
วี อาร์ 1000 - พีNiclosamide (1 G) + Phenolphthalein (100 MG)Tabletบริษัท เอช.เค.ฟาร์มาซูติคอล จำกัด2015-11-18Not applicableThailand flag
วี.อาร์. 1000Niclosamide (1 g) + Phenolphthalein (100 mg)Tabletบริษัท เอช.เค.ฟาร์มาซูติคอล จำกัด2015-11-18Not applicableThailand flag

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
Affected organisms
  • Helminthic Microorganisms

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
PDBe Ligand
VUT
Drugs.com
Drugs.com Drug Page
Wikipedia
Niclosamide
PDB Entries
8sur

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedScreeningTaenia Solium Taeniasis1somestatusstop reasonjust information to hide
Not AvailableTerminatedTreatmentIntestinal Parasitism1somestatusstop reasonjust information to hide
4CompletedTreatmentCoronavirus Disease 2019 (COVID‑19) / Treatment Efficacy1somestatusstop reasonjust information to hide
3CompletedTreatmentDiabetic Nephropathy1somestatusstop reasonjust information to hide
3Unknown StatusTreatmentCoronavirus Disease 2019 (COVID‑19)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral500 mg
Tablet, chewableOral500 mg
Tablet500 mg
Tablet
Tablet1000 mg
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 Area92.47 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity79.5 m3·mol-1Chemaxon
Polarizability28.52 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-MSsplash10-0udi-6901000000-2b365b023e021b160f32
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0006-2920000000-abe97627fbae89daa0db
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
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-167.3961475
predicted
DarkChem Lite v0.1.0
[M-H]-160.0719791
predicted
DarkChem Lite v0.1.0
[M-H]-164.97795
predicted
DeepCCS 1.0 (2019)
[M+H]+167.1801475
predicted
DarkChem Lite v0.1.0
[M+H]+171.7897993
predicted
DarkChem Lite v0.1.0
[M+H]+167.33595
predicted
DeepCCS 1.0 (2019)
[M+Na]+166.2223475
predicted
DarkChem Lite v0.1.0
[M+Na]+166.3987475
predicted
DarkChem Lite v0.1.0
[M+Na]+174.74257
predicted
DeepCCS 1.0 (2019)

Targets

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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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data limited to in vitro studies.
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 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. [Article]

Drug created at September 14, 2010 16:21 / Updated at June 19, 2021 00:26