NITAZOXANIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H9N3O5S
Molecular Weight	307.282
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)OC1=CC=CC=C1C(=O)NC2=NC=C(S2)[N+]([O-])=O

InChI

InChIKey=YQNQNVDNTFHQSW-UHFFFAOYSA-N

InChI=1S/C12H9N3O5S/c1-7(16)20-9-5-3-2-4-8(9)11(17)14-12-13-6-10(21-12)15(18)19/h2-6H,1H3,(H,13,14,17)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021818lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/21397502
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25762088 https://www.ncbi.nlm.nih.gov/pubmed/20404119 https://www.ncbi.nlm.nih.gov/pubmed/17888524

Tizoxanide, the primary active metabolite of the FDA approved drug nitazoxanide, an anti-infective that has been approved for the treatment of diarrhea caused by Giardia lamblia. Tizoxanide, an active metabolite of nitazoxanide in humans, is also an antiparasitic drug of the thiazolide class. It has broad-spectrum antiparasitic and broad-spectrum antiviral properties. Besides, it has being found that Tizoxanide exhibits appreciable antagonist activity for both mGluR1 and mGluR5 (IC50 = 1.8 uM and 1.2 uM, respectively).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pyruvate:ferredoxin oxidoreductase 3 Target ID: CHEMBL2364027 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021818lbl.pdf	Inhibitor 8504
Mycobacterium tuberculosis 21 Target ID: CHEMBL360 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27156623	Inhibitor 8504
Metabotropic glutamate receptor 1 25 Target ID: CHEMBL3772 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25762088	Antagonist 2849	1.8 µM [IC50]
Metabotropic glutamate receptor 5 40 Target ID: CHEMBL3227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25762088	Antagonist 2849	1.2 µM [IC50]
Rotavirus 2 Target ID: CHEMBL613722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23926336	Inhibitor 8504
Giardia intestinalis 2 Target ID: CHEMBL612652 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21397502	Inhibitor 8504	0.716 µM [IC50]
Trichomonas vaginalis 11 Target ID: CHEMBL612884 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21397502	Inhibitor 8504	0.211 µM [IC50]
Staphylococcus aureus 70 Target ID: CHEMBL352 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20404119	Inhibitor 8504
Hepatitis B virus 8 Target ID: CHEMBL613497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888524	Inhibitor 8504	0.15 µM [EC50]
Pyruvate:ferredoxin oxidoreductase 3 Target ID: CHEMBL2364026 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021818lbl.pdf	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Diarrhea caused by Giardia lamblia or Cryptosporidium parvum 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021818lbl.pdf	Curative	Approved 8583	ALINIA Approved Use Diarrhea caused by Giardia lamblia or Cryptosporidium parvum: Alinia for Oral Suspension (patients 1 year of age and older) and Alinia Tablets (patients 12 years and older) are indicated for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum. Alinia for Oral Suspension and Alinia Tablets have not been shown to be superior to placebo for the treatment of diarrhea caused by Cryptosporidium parvum in HIV-infected or immunodeficient patients (see CLINICAL STUDIES ). Launch Date 2004
Rotavirus gastroenteritis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23926336	Primary	Basic research	Unknown Approved Use Unknown
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27156623 https://www.ncbi.nlm.nih.gov/pubmed/22589723	Curative	Basic research	Unknown Approved Use Unknown
Trichomoniasis 18 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11751773 https://www.ncbi.nlm.nih.gov/pubmed/21397502	Curative	Basic research	Unknown Approved Use Unknown
Hepatitis B 59 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888524	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6.795 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22533565	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIZOXANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIZOXANIDE plasma	Homo sapiens population: UNKNOWN age: ADOLESCENT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
27.23 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22533565	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIZOXANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
39.5 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIZOXANIDE plasma	Homo sapiens population: UNKNOWN age: ADOLESCENT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.38 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22533565	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIZOXANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIZOXANIDE plasma	Homo sapiens population: UNKNOWN age: ADOLESCENT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
4 mg 1 times / day steady, oral MTD Dose: 4 mg, 1 times / day Route: oral Route: steady Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/	healthy, adult Health Status: healthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/	Other AEs: Gastrointestinal disorders NEC... Other AEs: Gastrointestinal disorders NEC Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/

AEs

AE	Significance	Dose	Population
Gastrointestinal disorders NEC		4 mg 1 times / day steady, oral MTD Dose: 4 mg, 1 times / day Route: oral Route: steady Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/	healthy, adult Health Status: healthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 110 CYP1A2 2153 CYP2C19 2057 CYP2B6 926 CYP2E1 1060 CYP3A5 136

Drug as perpetrator

Target	Modality	Activity
CYP 150	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf Page: 8.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 16.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 16.0	no
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 16.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	weak [IC50 >100 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	weak

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY531640	https://www.001chemical.com/chem/173903-47-4
AA Blocks	AA001Z6T	https://www.aablocks.com/goods/Goods/detail?id=AA001Z6T
Aaron Chemicals	AR001ZYL	http://www.aaronchem.com/173903-47-4
abcr GmbH	AB464410	http://www.abcr.com/shop/en/AB464410
Acadechem	ACDS-046361	http://www.acadechemical.com/product/121060
Achemo Scientific Limited	AC-94847	http://www.achemo.com/search/?Keyword=173903-47-4
AK Scientific, Inc. (AKSCI)	8987AA	http://www.aksci.com/item_detail.php?cat=8987AA
Angel Pharmatech	AG-11627	http://www.angelpharmatech.com/173903-47-4.html
Anward	ANW-60134	http://www.anward.com/pro_result/46585
Ark Pharm	AK-60881	http://www.arkpharminc.com/products/173903-47-4.html
Ark Pharma Scientific Limited	A-0871	http://www.arkpharmtech.com/product/32822.html
Aurum Pharmatech LLC	NE62763	http://www.Aurumpharmatech.com/Product/ProductDetails/NE62763
BioChemPartner	BCP08678	http://www.biochempartner.com/173903-47-4-BCP08678
BioSynth	J-010949	https://www.biosynth.com/en/products/all-products/products/J-010949.html
BLD Pharm	BD208327	http://www.bldpharm.com/products/173903-47-4.html
Capot Chemical	20794	http://www.capotchem.com/en/20794.htm
Capot Chemical	PubChem20794	http://www.capotchem.com/en/20794.htm
Chem Scene	CS-3893	http://www.chemscene.com/173903-47-4.html
Chemspace	CSSB00015203979	https://chem-space.com/CSSB00015203979
Clearsynth	CS-T-44466	https://www.clearsynth.com/en/CST44466.html
CSNpharm	CSN12663	https://www.csnpharm.com/products/tizoxanide.html
DC Chemicals	DC8336	http://www.dcchemicals.com/product_show-Tizoxanide.html
Debye Scientific	DB-064924	http://www.debyesci.com/cas_173903-47-4.html
eNovation Chemicals	D544470	https://www.enovationchem.com/ProductDetails.asp?ProductID=D544470
eNovation Chemicals	D952630	https://www.enovationchem.com/ProductDetails.asp?ProductID=D952630
eNovation Chemicals	Y0974571	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974571
eNovation Chemicals	Y1008359	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1008359
Finetech	FT-0675256	http://www.finetechnology-ind.com/prod/detail/pub/173903-47-4.html
J&W PharmLab	90R0384	https://www.jwpharmlab.com/home/product/90R0384
Lab Network	LN00195447	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00195447
Matrix Scientific	94509	https://www.matrixscientific.com/094509.html
MedChem Express	HY-12687	https://www.medchemexpress.com/Tizoxanide.html
Molcore	MC531640	https://www.molcore.com/product/173903-47-4
Oakwood	44549	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=38424&ExtHyperLink=1
Sinfoo Biotech	S030704	http://www.sinfoobiotech.com/product/1034102
Smolecule	S545437	http://www.smolecule.com/products/s545437
Smolecule	S775909	https://www.smolecule.com/products/s775909
Synblock Inc	SB34253	http://www.synblock.com/product/173903-47-4.html
THE BioTek	bt-285752	https://www.thebiotek.com/product/inhibitors/bt-285752

PubMed

Title	Date	PubMed
Nitazoxanide in the treatment of amoebiasis.	2007-10	17658567
Clostridium difficile: new therapeutic options.	2007-10	17644040
Failure of nitazoxanide to cure trichomoniasis in three women.	2007-10	17551415
Nitazoxanide in the treatment of Ascaris lumbricoides in a rural zone of Colima, Mexico.	2007-09	17594741
Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole.	2007-08	17561498
Induction of tachyzoite egress from cells infected with the protozoan Neospora caninum by nitro- and bromo-thiazolides, a class of broad-spectrum anti-parasitic drugs.	2007-08	17481636
Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.	2007-07-18	17636768
Clostridium difficile: recent epidemiologic findings and advances in therapy.	2007-07	17594209
In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells.	2007-07	17306057
Isolated gastric cryptosporidiosis in an immunocompetent patient.	2007-05	17372826
Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.	2007-04	17337513
Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis.	2007-04	17335543
Is nitazoxanide an effective treatment for patients with acquired immune deficiency syndrome-related cryptosporidiosis?	2007-03	17245327
Efficacy of nitazoxanide for cyclosporiasis in patients with sulfa allergy.	2007-02-01	17205465
Nitazoxanide or CD3+/CD4+ lymphocytes for recovery from severe Cryptosporidium infection after allogeneic bone marrow transplant?	2007-02	17239134
Severe cryptosporidiosis in a seven-year-old renal transplant recipient: case report and review of the literature.	2007-02	17239130
Structure-activity relationships from in vitro efficacies of the thiazolide series against the intracellular apicomplexan protozoan Neospora caninum.	2007-02	17141783
Efficacy of nitazoxanide, tizoxanide and tizoxanide/albendazole sulphoxide combination against Taenia crassiceps cysts.	2007-02	17114175
Hymenolepis nana infection: symptoms and response to nitazoxanide in field conditions.	2007-02	16814334
[New drugs against parasitic diseases].	2007-01-31	17432522
Prevention and treatment of cryptosporidiosis in immunocompromised patients.	2007-01-24	17253532
Nitazoxanide versus metronidazole for Clostridium difficile-associated colitis.	2007-01-01	17143841
Past, present, and future therapies for Clostridium difficile-associated disease.	2006-12	17148650
Emerging therapies in the treatment of Clostridium difficile-associated disease.	2006-12	17119105
Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial.	2006-11-15	17081163
Antimicrobial therapy of Clostridium difficile-associated diarrhea.	2006-11	17116441
Nitazoxanide in the treatment of acquired immune deficiency syndrome-related cryptosporidiosis: results of the United States compassionate use program in 365 patients.	2006-09-01	16918894
Nitazoxanide for the treatment of Clostridium difficile colitis.	2006-08-15	16838229
[Development of novel antihelminthic therapies].	2006-08	16999038
[Therapeutic alternatives in case of failure of first-line treatment of intestinal helminthiasis in adults].	2006-08	16999037
Current status of anti-diarrheal and anti-secretory drugs in the management of acute childhood diarrhea.	2006-08	16936364
Treatment options for the eradication of intestinal protozoa.	2006-08	16883348
Effect of nitazoxanide for treatment of severe rotavirus diarrhoea: randomised double-blind placebo-controlled trial.	2006-07-08	16829296
Nitazoxanide for rotavirus diarrhoea?	2006-07-08	16829280
An update on diagnosis, treatment, and prevention of Clostridium difficile-associated disease.	2006-06	16880068
Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections.	2006-05	16634717
Practical considerations of new drugs: new choices for old problems.	2006-04	16669748
Effect of nitazoxanide in diarrhea and enteritis caused by Cryptosporidium species.	2006-03	16527695
Use of nitazoxanide for gastrointestinal tract infections: treatment of protozoan parasitic infection and beyond.	2006-03	16524544
Efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model.	2006-02	16361328
14-3-3- and II/3-10-gene expression as molecular markers to address viability and growth activity of Echinococcus multilocularis metacestodes.	2006-01	16393357
Molecular survival strategies of Echinococcus multilocularis in the murine host.	2006	16352460
Nitazoxanide.	2005-11	16340060
Effect of nitazoxanide in persistent diarrhea and enteritis associated with Blastocystis hominis.	2005-10	16234044
Treatment of cryptosporidiosis in immunocompromised hosts.	2005-07	16006765
Use of nitazoxanide as a new therapeutic option for persistent diarrhea: a pediatric perspective.	2005-07	16004666
Nitazoxanide for treatment of intestinal parasites in children.	2005-07	15999008
Evaluation of the in vitro effect of albendazole, metronidazole and nitazoxanide on viability and structure of Giardia lamblia cysts.	2005-05-24	15906598
Nitazoxanide: a new thiazolide antiparasitic agent.	2005-04-15	15791519
Nitazoxanide for persistent diarrhoea in Zambian acquired immune deficiency syndrome patients: a randomized-controlled trial.	2005-03-15	15771762

Patents

Sample Use Guides

In Vivo Use Guide

Nitazoxanide treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum: 1-3 years old patients: 5 mL of Alinia for Oral Suspension (100 mg nitazoxanide) every 12 hourswith food for 3 days; 4-11 years old patients: 10 mL of Alinia for Oral Suspension (200 mg nitazoxanide) every 12 hours with food for 3 days; ≥12 years old patients: 1 Alinia Tablet (500 mg nitazoxanide) every 12 hours with food or 25 mL of Alinia for Oral Suspension (500 mg nitazoxanide) every 12 hours with food for 3 days

Route of Administration: Oral

In Vitro Use Guide

Nitazoxanide and its metabolites tizoxanide and tizoxanide glucuronide were inhibitory for up to 46 h when added after Cryptosporidium parvum sporozoite invasion in differentiated human enterocytic HCT-8 cells (MIC50 1.2, 22.6 and 2.2 mg/L, respectively).

Name

Type

Language

NITAZOXANIDE

Official Name

English

ALINIA

Preferred Name

English

NITAZOXANIDE [GREEN BOOK]

Common Name

English

NITAZOXANIDE [VANDF]

Common Name

English

nitazoxanide [INN]

Common Name

English

NITAZOXANIDE [ORANGE BOOK]

Common Name

English

NSC-760057

Code

English

NITAZOXANIDE [MI]

Common Name

English

Nitazoxanide [WHO-DD]

Common Name

English

NITAZOXANIDE [USP-RS]

Common Name

English

PH 5776

Code

English

N-(5-Nitrothiazol-2-yl)salicylamide acetate ester

Common Name

English

NITAZOXANIDE [USAN]

Common Name

English

NSC-697855

Code

English

BENZAMIDE, 2-(ACETYLOXY)-N-(5-NITRO-2-THIAZOLYL)-

Systematic Name

English

PH-5776

Code

English

NITAZOXANIDE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C277