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=C(C=CC=C1)C(=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

Molecular Formula	C12H9N3O5S
Molecular Weight	307.282
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21397502http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021818lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15791519 http://www.romark.com/about-romark/history

Nitazoxanide is a new thiazolide antiparasitic agent that shows excellent in vitro activity against a wide variety of protozoa and helminths. In 1993, Dr. Jean-François Rossignol and investor/partner Marc Ayers co-founded Romark Laboratories, L.C., to develop Rossignol's invention, nitazoxanide, as a treatment for Cryptosporidium infection and to discover and develop other new small molecule drugs in the same class called the thiazolides. In 2002, Alinia® (nitazoxanide) suspension was approved by the FDA for treating diarrhea caused by Cryptosporidium parvum and Giardia lamblia in children. Alinia® tablets were approved by the FDA in July 2004. It is given by the oral route with good bioavailability and is well tolerated, with primarily mild gastrointestinal side effects. Following oral administration in humans, nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide). Tizoxanide then undergoes conjugation, primarily by glucuronidation. The antiprotozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. Studies have shown that the PFOR enzyme from Giardia lamblia directly reduces nitazoxanide by transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of Cryptosporidium parvum appears to be similar to that of Giardia lamblia. Interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity.

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 8228
Mycobacterium tuberculosis 20 Target ID: CHEMBL360 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27156623	Inhibitor 8228
Metabotropic glutamate receptor 1 26 Target ID: CHEMBL3772 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25762088	Antagonist 2760	1.8 µM [IC50]
Metabotropic glutamate receptor 5 39 Target ID: CHEMBL3227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25762088	Antagonist 2760	1.2 µM [IC50]
Rotavirus 2 Target ID: CHEMBL613722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23926336	Inhibitor 8228
Giardia intestinalis 2 Target ID: CHEMBL612652 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21397502	Inhibitor 8228	0.716 µM [IC50]
Trichomonas vaginalis 11 Target ID: CHEMBL612884 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21397502	Inhibitor 8228	0.211 µM [IC50]
Staphylococcus aureus 65 Target ID: CHEMBL352 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20404119	Inhibitor 8228
Hepatitis B virus 8 Target ID: CHEMBL613497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888524	Inhibitor 8228	0.15 µM [EC50]
Pyruvate:ferredoxin oxidoreductase 3 Target ID: CHEMBL2364026 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021818lbl.pdf	Inhibitor 8228

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 8360	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 1.09036798E12
Rotavirus gastroenteritis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23926336	Primary	Basic research	Unknown Approved Use Unknown
Tuberculosis 81 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 54 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888524	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

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/ Page: 1	healthy, adult n = 6 Health Status: healthy Age Group: adult Sex: unknown Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/ Page: 1	Other AEs: Gastrointestinal disorders NEC... Other AEs: Gastrointestinal disorders NEC Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/ Page: 1

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/ Page: 1	healthy, adult n = 6 Health Status: healthy Age Group: adult Sex: unknown Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12051573/ Page: 1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 110 CYP1A2 1509 CYP2C19 1463 CYP2B6 799 CYP2E1 876 CYP3A5 73

Drug as perpetrator

Target	Modality	Activity
CYP 146	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf Page: 8.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 16.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 16.0	no
CYP3A5 130	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 16.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021818s000_ClinPharmR.pdf Page: 8.0	weak [IC50 >100 uM]
CYP3A4 1909	inhibitor 3240 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
AK Scientific, Inc. (AKSCI)	8987AA	http://www.aksci.com/item_detail.php?cat=8987AA
Aaron Chemicals	AR001ZYL	http://www.aaronchem.com/173903-47-4
Acadechem	ACDS-046361	http://www.acadechemical.com/product/121060
Achemo Scientific Limited	AC-94847	http://www.achemo.com/search/?Keyword=173903-47-4
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
BLD Pharm	BD208327	http://www.bldpharm.com/products/173903-47-4.html
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
CSNpharm	CSN12663	https://www.csnpharm.com/products/tizoxanide.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
DC Chemicals	DC8336	http://www.dcchemicals.com/product_show-Tizoxanide.html
Debye Scientific	DB-064924	http://www.debyesci.com/cas_173903-47-4.html
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
abcr GmbH	AB464410	http://www.abcr.com/shop/en/AB464410
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

PubMed

Title	Date	PubMed
Screening of compounds for antimicrosporidial activity in vitro.	1998	9684323
In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis.	2002 Jan	11751773
Nitazoxanide as a broad-spectrum antiparasitic agent.	2002 Jun 1	12023782
Nitazoxanide compared with quinfamide and mebendazole in the treatment of helminthic infections and intestinal protozoa in children.	2002 Mar	12139216
Treatment of intestinal parasitic infections: a review of nitazoxanide.	2002 Mar	11854075
Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru.	2002 Mar-Apr	12055813
In vitro effect of nitazoxanide against Entamoeba histolytica, Giardia intestinalis and Trichomonas vaginalis trophozoites.	2002 May-Jun	12120985
Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial.	2002 Nov 2	12423984
Cryptosporidiosis.	2002 Oct	12686887
In-vitro transfer of nitazoxanide across the intestinal epithelial barrier.	2002 Oct	12396305
Nitazoxanide (Alinia)--a new anti-protozoal agent.	2003 Apr 14	12717338
Double-blind, randomized, placebo-controlled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru.	2003 Jan	12534412
New drugs 04, part 1.	2004 Feb	14758333
[Nitazoxanide vs albendazole against intestinal parasites in a single dose and for three days].	2004 Jul-Aug	15468574
New drugs of 2003.	2004 Mar-Apr	15098851
Parasitic infections.	2004 Nov	15504227
[Nitazoxanide: adverse effects].	2004 Nov-Dec	15624851
In vitro effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes.	2004 Sep	15282238
Treatment of cryptosporidiosis in immunocompromised hosts.	2005 Jul	16006765
Use of nitazoxanide as a new therapeutic option for persistent diarrhea: a pediatric perspective.	2005 Jul	16004666
Nitazoxanide for treatment of intestinal parasites in children.	2005 Jul	15999008
Nitazoxanide.	2005 Nov	16340060
Effect of nitazoxanide in persistent diarrhea and enteritis associated with Blastocystis hominis.	2005 Oct	16234044
Molecular survival strategies of Echinococcus multilocularis in the murine host.	2006	16352460
Past, present, and future therapies for Clostridium difficile-associated disease.	2006 Dec	17148650
Emerging therapies in the treatment of Clostridium difficile-associated disease.	2006 Dec	17119105
Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial.	2006 Nov 15	17081163
Bioequivalence study of a fixed dose combination of nitazoxanide and ofloxacin in Indian healthy volunteers.	2007	18074762
Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.	2007 Apr	17337513
Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis.	2007 Apr	17335543
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 Aug	17481636
Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole.	2007 Aug	17561498
Nitazoxanide or CD3+/CD4+ lymphocytes for recovery from severe Cryptosporidium infection after allogeneic bone marrow transplant?	2007 Feb	17239134
Severe cryptosporidiosis in a seven-year-old renal transplant recipient: case report and review of the literature.	2007 Feb	17239130
Efficacy of nitazoxanide for cyclosporiasis in patients with sulfa allergy.	2007 Feb 1	17205465
Prevention and treatment of cryptosporidiosis in immunocompromised patients.	2007 Jan 24	17253532
[New drugs against parasitic diseases].	2007 Jan 31	17432522
Clostridium difficile: recent epidemiologic findings and advances in therapy.	2007 Jul	17594209
Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.	2007 Jul 18	17636768
Is nitazoxanide an effective treatment for patients with acquired immune deficiency syndrome-related cryptosporidiosis?	2007 Mar	17245327
Failure of nitazoxanide to cure trichomoniasis in three women.	2007 Oct	17551415
Nitazoxanide in the treatment of Ascaris lumbricoides in a rural zone of Colima, Mexico.	2007 Sep	17594741
Neospora caninum: functional inhibition of protein disulfide isomerase by the broad-spectrum anti-parasitic drug nitazoxanide and other thiazolides.	2008 Jan	17720161
Liquid chromatography-tandem mass spectrometry analysis of nitazoxanide and its major metabolites in goat.	2008 Nov 15	18849204
Nitazoxanide, tizoxanide and a new analogue [4-nitro-N-(5-nitro-1,3-thiazol-2-yl)benzamide; NTB] inhibit the growth of kinetoplastid parasites (Trypanosoma cruzi and Leishmania mexicana) in vitro.	2009 Jun	19346519
Prophylactic and therapeutic efficacy of nitazoxanide against Cryptosporidium parvum in experimentally challenged neonatal calves.	2009 Mar 9	19062195
Hepatitis C and kidney disease.	2010	21188196
In Vitro Susceptibility of Canine Influenza A (H3N8) Virus to Nitazoxanide and Tizoxanide.	2010 Aug 12	20847948
Antiviral treatment of chronic hepatitis B virus (HBV) infections.	2010 Jun	21994680
New treatments for chronic hepatitis C.	2010 Sep	20924208

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

In mycobacterial growth indicator tube [MGIT] cultures inhibition of Mycobacterium tuberculosis growth occurred at total drug concentrations of ≥16 ug/ml (almost complete inhibition of growth was achieved at 64 ug/ml), whereas in whole blood cultures (albumin concentration = 350 uM), ≥128 ug/ml was required.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:54:11 UTC 2023` Edited by `admin` on `Wed Jul 05 23:54:11 UTC 2023`
Record UNII	SOA12P041N
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NITAZOXANIDE

Official Name

English

NITAZOXANIDE [GREEN BOOK]

Common Name

English

ALINIA

Brand 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