U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C22H14Cl2I2N2O2
Molecular Weight 663.074
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLOSANTEL

SMILES

CC1=CC(C(C#N)C2=CC=C(Cl)C=C2)=C(Cl)C=C1NC(=O)C3=C(O)C(I)=CC(I)=C3

InChI

InChIKey=JMPFSEBWVLAJKM-UHFFFAOYSA-N
InChI=1S/C22H14Cl2I2N2O2/c1-11-6-15(17(10-27)12-2-4-13(23)5-3-12)18(24)9-20(11)28-22(30)16-7-14(25)8-19(26)21(16)29/h2-9,17,29H,1H3,(H,28,30)

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including http://parasitipedia.net/index.php?option=com_content&view=article&id=2505&Itemid=2778

Closantel is a synthetic anti parasitic agent which is highly effective against adults and larvae (6 to weeks old) of liver flukes (Fasciola hepatica), and against several important gastrointestinal roundworms (e.g. Bunostomum, Haemonchus, Oesophagostomum, Ostertagia - Teladorsagia, Strongyloides, Trichostrongylus), as well as against screwworms (maggots of Cochliomyia spp and Chrysomya spp), sheep nasal bots (Oestrus ovis), and sheep keds (Melophagus ovinus). The molecular mode of action closantel is not completely elucidated, but closantel decouples the mitochondrial oxidative phosphorylation, which leads to the inhibition of ATP synthesis, this seems to occur through suppression of the activity of succinate dehydrogenase and fumarate reductase, two enzymes involved in this process. Finally this all cause the death of the parasite. Recently it has been discovered that closantel also inhibits chitinase in Onchocerca volvulus, a filarial nematode causing river blindness in humans. Chitinase is an enzyme involved in larval molting. Its inhibition interrupts their development to adult worms. This drug possesses some side effects: hyper acute anaphylactic reactions in cattle; hypersensitivity reactions; overdoses can cause reduced visibility or blindness, anorexia, lack of coordination and general weakness.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
CLOSANTEL

Approved Use

for veterinary use on CATTLE, SHEEP and GOATS against flukes, roundworms and myiases
Curative
CLOSANTEL

Approved Use

for veterinary use on CATTLE, SHEEP and GOATS against flukes, roundworms and myiases
Curative
CLOSANTEL

Approved Use

for veterinary use on CATTLE, SHEEP and GOATS against flukes, roundworms and myiases
PubMed

PubMed

TitleDatePubMed
Reduced efficacy of ivermectin, abamectin and moxidectin against field isolates of Haemonchus contortus.
2001 Dec
Anthelmintic resistance on an organized sheep farm in India.
2001 Jul
Blindness in lambs due to inadvertent closantel overdose.
2002 Jul 6
Strategic use of moxidectin or closantel in combination with levamisole in the control of nematodes of sheep in the highlands of central Kenya.
2002 Nov
Strategic control of gastrointestinal nematodes of sheep in the highlands of central Kenya.
2002 Sep
The relationship between nasal myiasis and the prevalence of enzootic nasal tumours and the effects of treatment of Oestrus ovis and milk production in dairy ewes of Roquefort cheese area.
2003 Apr 18
Evolution of high-level, multiple anthelmintic resistance on a sheep farm in Malaysia.
2003 Feb
Field trial on the efficacy of an experimental fasciolicide compared with some commercial compounds in naturally infected cattle.
2003 Sep
Epidemiology of Oestrus ovis infection of sheep in Argentina's Western Pampas.
2004 Dec
Rift Valley fever in small ruminants, Senegal, 2003.
2005 Nov
Anthelmintic activity of Azadirachta indica A. Juss against sheep gastrointestinal nematodes.
2006 Apr 30
Intra-leukocyte expression of two-component systems in Ehrlichia chaffeensis and Anaplasma phagocytophilum and effects of the histidine kinase inhibitor closantel.
2006 Aug
Pharmacokinetics of a novel closantel/ivermectin injection in cattle.
2006 Jun
Analysis of OSPAR priority pharmaceuticals using high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry.
2006 Nov 17
The effect of a parenteral ivermectin/closantel injection on the growth and reproductive development of early immature Fasciola hepatica in cattle.
2006 Nov 30
Closantel toxicosis in kid goats.
2006 Oct 21
Validated method for determination of ultra-trace closantel residues in bovine tissues and milk by solid-phase extraction and liquid chromatography-electrospray ionization-tandem mass spectrometry.
2007 Dec 21
Myelin vacuolation, optic neuropathy and retinal degeneration after closantel overdosage in sheep and in a goat.
2007 Feb-Apr
Purification, reconstitution, and characterization of the CpxRAP envelope stress system of Escherichia coli.
2007 Mar 23
Determination of closantel residues in milk and animal tissues by HPLC with fluorescence detection and SPE with oasis MAX cartridges.
2008 Apr
The efficacy of an ivermectin/closantel injection against experimentally induced infections and field infections with gastrointestinal nematodes and liver fluke in cattle.
2008 Aug 17
A comparison of the efficacy of doramectin, closantel and levamisole in the treatment of the 'oriental eye fluke', Philophthalmus gralli, in commercially reared ostriches (Struthio camelus).
2008 Jun
Efficacy of 3 anthelmintics in communally grazed sheep as reflected by faecal egg count reduction tests in a semi-arid area of South Africa.
2008 Mar
[Evaluation of the efficacy of antihelmintics compounds on parasitics gastrointestinal nematodes (Strongyloidea) of goats].
2008 Sep
Comparison of the time required to administer three different fluke and worm combination products to commercial beef cattle at housing.
2008 Spring
Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.
2009 Jul 14
The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles.
2009 Jun 10
Multi-residue determination of phenolic and salicylanilide anthelmintics and related compounds in bovine kidney by liquid chromatography-tandem mass spectrometry.
2009 Nov 13
The comparative efficacy of four anthelmintics against a natural acquired Fasciola hepatica infection in hill sheep flock in the west of Ireland.
2009 Oct 14
Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.
2009 Sep 22
Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells.
2010 Aug 5
Multiple resistance to anthelmintics by Haemonchus contortus and Trichostrongylus colubriformis in sheep in Brazil.
2010 Dec
Screening of closantel and rafoxanide in animal muscles by HPLC with fluorescence detection and confirmation using MS.
2010 Feb
Unchanged triclabendazole kinetics after co-administration with ivermectin and methimazole: failure of its therapeutic activity against triclabendazole-resistant liver flukes.
2010 Feb 3
Polioencephalomalacia associated with closantel overdosage in a goat.
2010 Jun
Assay strategies for the discovery and validation of therapeutics targeting Brugia pahangi Hsp90.
2010 Jun 15
Anthelmintic efficacy and management practices in sheep farms from the state of Rio de Janeiro, Brazil.
2010 Jun 24
A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility.
2010 Nov 16
Nasal bots...a fascinating world!
2010 Nov 24
Multiple resistance of gastrointestinal nematodes to nine different drugs in a sheep flock in southern Brazil.
2010 Oct 11
Quantitative analysis of closantel and rafoxanide in bovine and ovine muscles by high-performance liquid chromatography with fluorescence detection.
2010 Sep-Oct
Design, synthesis, and biological activities of closantel analogues: structural promiscuity and its impact on Onchocerca volvulus.
2011 Jun 9
An improved thyroid hormone reporter assay to determine the thyroid hormone-like activity of amiodarone, bithionol, closantel and rafoxanide.
2012 Jan 5
Patents

Patents

Sample Use Guides

in animals: CATTLE Oral Gastrointestinal roundworms: 5-10 mg/kg; Oral Hypoderma spp: 10 mg/kg; Subcutaneous Gastrointestinal roundworms: 3 mg/kg; Subcutaneous Fasciola hepatica: 5 mg/kg; SHEEP: Oral Gastrointestinal roundworms: 5-10 mg/kg; Oral Oestrus ovis: 5 mg/kg; Oral Fasciola hepatica: 10 mg/kg; Subcutaneous Gastrointestinal roundworms: 5-10 mg/kg; GOATS: Oral Gastrointestinal roundworms: 10 mg/kg; Subcutaneous Gastrointestinal roundworms: 5 mg/kg
Route of Administration: Other
In Vitro Use Guide
Unknown
Name Type Language
CLOSANTEL
INN   MART.   MI   USAN  
USAN   INN  
Official Name English
closantel [INN]
Common Name English
N-(5-CHLORO-4-((4-CHLOROPHENYL)CYANOMETHYL)-2-METHYLPHENYL)-2-HYDROXY-3,5-DIIODOBENZAMIDE
Systematic Name English
CLOSANTEL [USAN]
Common Name English
R-31520
Code English
BENZAMIDE, N-(5-CHLORO-4-((4-CHLOROPHENYL)CYANOMETHYL)-2-METHYLPHENYL)-2-HYDROXY-3,5-DIIODO-
Systematic Name English
CLOSANTEL [MART.]
Common Name English
R 31,520
Code English
CLOSANTEL [MI]
Common Name English
(RS)-5'-CHLORO-4'-(4-CHLORO-.ALPHA.-CYANOBENZYL)-3,5-DIIODOSALICYL-O-TOLUIDIDE
Common Name English
NSC-335306
Code English
Classification Tree Code System Code
NCI_THESAURUS C250
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
WHO-VATC QP52AG09
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
Code System Code Type Description
NSC
335306
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
PRIMARY
CAS
57808-65-8
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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NCI_THESAURUS
C79920
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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FDA UNII
EUL532EI54
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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MERCK INDEX
m3666
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
PRIMARY Merck Index
ChEMBL
CHEMBL12131
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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PUBCHEM
42574
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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EVMPD
SUB06769MIG
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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ALANWOOD
closantel
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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MESH
C023342
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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EPA CompTox
DTXSID6040662
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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CAS
57808-65-8
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
PRIMARY
INN
4049
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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CHEBI
77053
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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ECHA (EC/EINECS)
260-967-1
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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SMS_ID
100000084012
Created by admin on Fri Dec 15 16:12:40 GMT 2023 , Edited by admin on Fri Dec 15 16:12:40 GMT 2023
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