Identification
NameThiabendazole
Accession NumberDB00730  (APRD01252, DB08630)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

2-Substituted benzimidazole first introduced in 1962. It is active against a variety of nematodes and is the drug of choice for strongyloidiasis. It has CNS side effects and hepatototoxic potential. (From Smith and Reynard, Textbook of Pharmacology, 1992, p919)

Structure
Thumb
Synonyms
2-(1,3-THIAZOL-4-yl)-1H-benzimidazole
4-(2-Benzimidazolyl)thiazole
Equizole
TBDZ
Thiabendazole
Thibenzole
Tiabendazole
External IDs MK 360 / MK-360 / NSC-525040 / NSC-90507
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mintezol Chewable Tab 500mgTablet500 mgOralMerck Sharp & Dohme Limited1969-12-312000-08-03Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
MintezolNot Available
Brand mixturesNot Available
Categories
UNIIN1Q45E87DT
CAS number148-79-8
WeightAverage: 201.248
Monoisotopic: 201.036067929
Chemical FormulaC10H7N3S
InChI KeyWJCNZQLZVWNLKY-UHFFFAOYSA-N
InChI
InChI=1S/C10H7N3S/c1-2-4-8-7(3-1)12-10(13-8)9-5-14-6-11-9/h1-6H,(H,12,13)
IUPAC Name
2-(1,3-thiazol-4-yl)-1H-1,3-benzodiazole
SMILES
N1C2=CC=CC=C2N=C1C1=CSC=N1
Pharmacology
Indication

For the treatment of strongyloidiasis (threadworm), cutaneous larva migrans (creeping eruption), visceral larva migrans, and trichinosis.

Structured Indications Not Available
Pharmacodynamics

Thiabendazole is a fungicide and parasiticide. Thiabendazole is also a chelating agent, which means that it is used medicinally to bind metals in cases of metal poisoning, such as lead poisoning, mercury poisoning or antimony poisoning. Thiabendazole is vermicidal and/or vermifugal against Ascaris lumbricoides ("common roundworm"), Strongyloides stercoralis (threadworm), Necator americanus, Ancylostoma duodenale (hookworm), Trichuris trichiura (whipworm), Ancylostoma braziliense (dog and cat hookworm), Toxocara canis, Toxocara cati (ascarids), and Enterobius vermicularis (pinworm). Thiabendazole also suppresses egg and/or larval production and may inhibit the subsequent development of those eggs or larvae which are passed in the feces.

Mechanism of action

The precise mode of action of thiabendazole on the parasite is unknown, but it most likely inhibits the helminth-specific enzyme fumarate reductase.

TargetKindPharmacological actionActionsOrganismUniProt ID
Fumarate reductase flavoprotein subunitProteinyes
inhibitor
Escherichia coli (strain K12)P00363 details
Related Articles
Absorption

Rapidly absorbed and peak plasma concentration is reached within 1 to 2 hours after the oral administration of a suspension. Some systemic absorption may occur from topical preparations applied to the skin.

Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. Metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.

Route of elimination

It is metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.

Half life

The half-life for thiabendazole in both normal and anephric patients is 1.2 hours (range 0.9 to 2 hours). The half-life for the 5-hydroxythiabendazole metabolite in both normal and anephric patients is 1.7 hours (range 1.4 to 2 hours).

ClearanceNot Available
Toxicity

Overdosage may be associated with transient disturbances of vision and psychic alterations. The oral LD 50 is 3.6 g/kg, 3.1 g/kg and 3.8 g/kg in the mouse, rat, and rabbit respectively.

Affected organisms
  • Roundworms, hookworms, and other helminth species
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Thiabendazole can be increased when it is combined with Abiraterone.Approved
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Thiabendazole.Experimental
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Thiabendazole.Approved
AmodiaquineThe serum concentration of Thiabendazole can be decreased when it is combined with Amodiaquine.Approved
AzithromycinThe metabolism of Thiabendazole can be decreased when combined with Azithromycin.Approved
BortezomibThe metabolism of Thiabendazole can be decreased when combined with Bortezomib.Approved, Investigational
CaffeineThe metabolism of Thiabendazole can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of Thiabendazole can be increased when combined with Carbamazepine.Approved, Investigational
ChloroquineThe serum concentration of Thiabendazole can be decreased when it is combined with Chloroquine.Approved, Vet Approved
CitalopramThe metabolism of Thiabendazole can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of Thiabendazole can be decreased when combined with Clotrimazole.Approved, Vet Approved
Cyproterone acetateThe serum concentration of Thiabendazole can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of Thiabendazole can be increased when it is combined with Deferasirox.Approved, Investigational
DyphyllineThe metabolism of Dyphylline can be decreased when combined with Thiabendazole.Approved
FluvoxamineThe metabolism of Thiabendazole can be decreased when combined with Fluvoxamine.Approved, Investigational
HydroxychloroquineThe serum concentration of Thiabendazole can be decreased when it is combined with Hydroxychloroquine.Approved
LidocaineThe metabolism of Thiabendazole can be decreased when combined with Lidocaine.Approved, Vet Approved
MexiletineThe metabolism of Thiabendazole can be decreased when combined with Mexiletine.Approved
NevirapineThe metabolism of Thiabendazole can be decreased when combined with Nevirapine.Approved
OsimertinibThe serum concentration of Thiabendazole can be decreased when it is combined with Osimertinib.Approved
Peginterferon alfa-2bThe serum concentration of Thiabendazole can be increased when it is combined with Peginterferon alfa-2b.Approved
PhenobarbitalThe metabolism of Thiabendazole can be increased when combined with Phenobarbital.Approved
PrimaquineThe serum concentration of Thiabendazole can be decreased when it is combined with Primaquine.Approved
PrimidoneThe metabolism of Thiabendazole can be increased when combined with Primidone.Approved, Vet Approved
RifampicinThe metabolism of Thiabendazole can be increased when combined with Rifampicin.Approved
RopiniroleThe metabolism of Thiabendazole can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of Thiabendazole can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of Thiabendazole can be decreased when combined with Tenofovir.Approved, Investigational
TeriflunomideThe serum concentration of Thiabendazole can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Theophylline can be decreased when combined with Thiabendazole.Approved
TiclopidineThe metabolism of Thiabendazole can be decreased when combined with Ticlopidine.Approved
VemurafenibThe serum concentration of Thiabendazole can be increased when it is combined with Vemurafenib.Approved
Food InteractionsNot Available
References
Synthesis Reference

Lynn E. Applegate, Carl A. Renner, "Preparation of high purity thiabendazole." U.S. Patent US5310923, issued October, 1977.

US5310923
General ReferencesNot Available
External Links
ATC CodesD01AC06 — TiabendazoleP02CA02 — Tiabendazole
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (428 KB)
MSDSDownload (73.1 KB)
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
FormRouteStrength
TabletOral500 mg
Prices
Unit descriptionCostUnit
Thiabendazole powder1.27USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)300 °CPhysProp
water solubility50 mg/L (at 25 °C)WAUCHOPE,RD ET AL. (1991A)
logP2.47NIELSEN,LS ET AL. (1992)
pKa4.64 (at 25 °C)CHAMBERLAIN,K ET AL. (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.138 mg/mLALOGPS
logP2.47ALOGPS
logP2.33ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)10.28ChemAxon
pKa (Strongest Basic)4.08ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity64.91 m3·mol-1ChemAxon
Polarizability21.02 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9473
Caco-2 permeable-0.6733
P-glycoprotein substrateNon-substrate0.7174
P-glycoprotein inhibitor INon-inhibitor0.9299
P-glycoprotein inhibitor IINon-inhibitor0.9317
Renal organic cation transporterNon-inhibitor0.8624
CYP450 2C9 substrateNon-substrate0.8768
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.8103
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.5658
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8216
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6773
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9331
BiodegradationNot ready biodegradable0.9814
Rat acute toxicity2.0170 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9838
hERG inhibition (predictor II)Non-inhibitor0.9321
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Download (8.42 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0fk9-0950000000-6e07d9ba69360948a837View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0ufr-0690000000-b40f55bf077dd879267eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0059-0900000000-8eaacf527845d1846336View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-869b5011abd24f891c6fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0090000000-9f0e2f0e1206b841ba24View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0090000000-0b0912c87b5641d927e6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0090000000-79b8ef228f8ea67df5dfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0ufr-0590000000-79f15636fdcbfb8f2fdeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0fb9-0930000000-6c1cb6f8999732f4dfc8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0059-1900000000-f8df5dacb9aa1e2f51d2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0090000000-9815589c9344d01433c0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0090000000-6ec36e16db37eb084c0bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0490000000-80b3519b526efe662007View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0059-1910000000-679a1a2e18fa97997809View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-4900000000-a1599bcbfe1fe550efc3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-0ufr-0960000000-5883b4d0eb99d9d44922View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0ufr-1890000000-8fc66231bbe9a337b27bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-003r-2900000000-74f0c0bb9208bc4125beView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0190000000-89886baf5cc3c9c2ac6dView 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
MSMass Spectrum (Electron Ionization)splash10-0uk9-6960000000-9a4ba4c366b41681668eView in MoNA
1D NMR13C NMR SpectrumNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassBenzimidazoles
Direct ParentBenzimidazoles
Alternative ParentsBenzenoids / Thiazoles / Imidazoles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
SubstituentsBenzimidazole / Benzenoid / Heteroaromatic compound / Thiazole / Imidazole / Azole / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors1,3-thiazole, ring assembly, benzimidazoles, benzimidazole fungicide (CHEBI:45979 ) / Thiazole fungicides (C07131 ) / a small molecule (THIABENDAZOLE )

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Succinate dehydrogenase activity
Specific Function:
Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; the fumarate reductase is used in anaerobic growth, and the succinate dehydrogenase is used in aerobic growth.
Gene Name:
frdA
Uniprot ID:
P00363
Uniprot Name:
Fumarate reductase flavoprotein subunit
Molecular Weight:
65971.215 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Ge Z, Feng Y, Dangler CA, Xu S, Taylor NS, Fox JG: Fumarate reductase is essential for Helicobacter pylori colonization of the mouse stomach. Microb Pathog. 2000 Nov;29(5):279-87. [PubMed:11031122 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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
Uniprot Name:
Cytochrome P450 1A2
Molecular Weight:
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d 24-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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Uniprot Name:
Cytochrome P450 1A1
Molecular Weight:
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:31