OLTIPRAZ

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H6N2S3
Molecular Weight	226.342
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(SSC1=S)C2=CN=CC=N2

InChI

InChIKey=CKNAQFVBEHDJQV-UHFFFAOYSA-N

InChI=1S/C8H6N2S3/c1-5-7(12-13-8(5)11)6-4-9-2-3-10-6/h2-4H,1H3

HIDE SMILES / InChI

Molecular Formula	C8H6N2S3
Molecular Weight	226.342
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/20655236
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11303588 | https://clinicaltrials.gov/ct2/show/NCT02068339 | https://www.ncbi.nlm.nih.gov/pubmed/20095791 | https://clinicaltrials.gov/ct2/show/NCT00006457

Oltipraz is an organosulfur compound belonging to the dithiolethione class. It acts as a schistosomicide and has been shown in rodent models to inhibit the formation of cancers in the bladder, blood, colon, kidney, liver, lung, pancreas, stomach, and trachea, skin, and mammary tissue. Oltipraz and other 1,2-dithiole-3-thiones inactivate protein tyrosine phosphatases under physiologically-relevant conditions. Clinical trials of oltipraz have failed to demonstrate efficacy and have shown significant side effects, including neurotoxicity and gastrointestinal toxicity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Protein-tyrosine phosphatase 1B 34 Target ID: CHEMBL335 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20655236	Inhibitor 8504
Protein-tyrosine phosphatase 2C 2 Target ID: CHEMBL3864 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20655236	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Non-alcoholic fatty liver disease 32 Sources: https://clinicaltrials.gov/ct2/show/NCT02068339	Primary	Phase III 665	Unknown Approved Use Unknown
Liver fibrosis 9 Sources: https://clinicaltrials.gov/ct2/show/NCT00956098	Primary	Phase II 1147	Unknown Approved Use Unknown
Lung cancer 70 Sources: https://clinicaltrials.gov/ct2/show/NCT00006457	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
267 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815904/	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	OLTIPRAZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20664537/	90 mg 1 times / day steady-state, oral dose: 90 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	OLTIPRAZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
45 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20664537/	60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	OLTIPRAZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
50.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20664537/	60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	7-METHYL-6,8-BIS(METHYLTHIO)PYRROLO(1,2-A)PYRAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
37.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20664537/	90 mg 1 times / day multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered:	7-METHYL-6,8-BIS(METHYLTHIO)PYRROLO(1,2-A)PYRAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
463.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815904/	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:		OLTIPRAZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.95 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815904/	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:		OLTIPRAZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00IBSU	https://www.1pchem.com/search?query=1P00IBSU
AK Scientific	4440AJ	https://aksci.com/item_detail.php?cat=4440AJ
ApexBio Technology	B5958	https://www.apexbt.com/catalogsearch/result/?q=B5958
AstaTech	H10964	http://astatechinc.com/CPSResult.php?CRNO=H10964
BLD Pharm	BD146200	http://www.bldpharm.com/search/Search.html?keyword=BD146200
BOC Sciences	64224-21-1	http://www.bocsci.com/description.asp?cas=64224-21-1
Cayman Chemical	15118	http://www.caymanchem.com/app/template/Product.vm/catalog/15118
Chem Scene	CS-5412	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5412
ChemShuttle	152105	https://www.chemshuttle.com/catalogsearch/result/?q=152105
Chemspace	CSC000072803	https://chem-space.com/CSC000072803
eMolecules	744867	https://orderbb.emolecules.com/search/#?query=744867
Enamine	BBV-40203537	http://www.enaminestore.com/catalog/BBV-40203537
Excenen	EX-A646	http://www.excenen.com/searchresultlist.php?id=EX-A646
Hairui	HR143841	http://www.hairuichem.com/en/product/search.do?q=HR143841
KeyOrganics	AS-7036	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-7036
Lab Network	LN00203516	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00203516
Matrix Scientific	102868	http://www.matrixscientific.com/102868.html
mcule	MCULE-6441540374	https://mcule.com/MCULE-6441540374/
MedChem Express	HY-12519	https://www.medchemexpress.com/search.html?q=HY-12519&ft=&fa=&fp=
Molnova	M15443	https://www.molnova.com/en/serch-list.html?keywords=M15443
MolPort	MolPort-006-133-277	https://www.molport.com/shop/molecule-link/MolPort-006-133-277
MuseChem	I004425	https://www.musechem.com/product/I004425.html
Ryan Scientific	Proadifen_HCl	https://ryansci.com/products?q=Proadifen_HCl&list_q=&search_type=exact
Selleck Chemicals	S7864	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7864
ShangHai Biochempartner	BCP16064	http://www.biochempartner.com/search_BCP16064
TargetMol	T0153	https://www.targetmol.com/search?keyword=T0153
Tetrahedron	TS52381	http://www.thsci.com/search.do?q=TS52381
Tocris	5294	https://www.tocris.com/search.php?Type=QuickSearch&Value=5294
Toronto Research Chemicals	O586050	https://www.trc-canada.com/product-detail/?CatNum=O586050

PubMed

Title	Date	PubMed
Pharmacokinetics of oltipraz in rat models of diabetes mellitus induced by alloxan or streptozotocin.	2006-04-11	16288785
The phase 2 enzyme inducers ethacrynic acid, DL-sulforaphane, and oltipraz inhibit lipopolysaccharide-induced high-mobility group box 1 secretion by RAW 264.7 cells.	2006-03	16382025
Role of p90 ribosomal S6-kinase-1 in oltipraz-induced specific phosphorylation of CCAAT/enhancer binding protein-beta for GSTA2 gene transactivation.	2006-01	16246908
Modulation of apoptosis by cancer chemopreventive agents.	2005-12-11	16137721
Modulation of multigene expression and proteome profiles by chemopreventive agents.	2005-12-11	16083920
Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004.	2005-12	16330363
Oltipraz-induced phase 2 enzyme response conserved in cells lacking mitochondrial DNA.	2005-11-11	16188238
Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists.	2005-10	15917307
Enhanced CCAAT/enhancer-binding protein beta-liver-enriched inhibitory protein production by Oltipraz, which accompanies CUG repeat-binding protein-1 (CUGBP1) RNA-binding protein activation, leads to inhibition of preadipocyte differentiation.	2005-09	15961673
Regulation of mouse organic anion-transporting polypeptides (Oatps) in liver by prototypical microsomal enzyme inducers that activate distinct transcription factor pathways.	2005-09	15919853
Induction of phase-1 metabolizing enzymes by oltipraz, flavone and indole-3-carbinol enhance the formation and transport of benzo[a]pyrene sulfate conjugates in intestinal Caco-2 cells.	2005-08-14	15890477
Assessing the effect of interventions in the context of mixture distributions with detection limits.	2005-07-15	15803450
Effects of cysteine on the pharmacokinetics of oltipraz in rats with protein-calorie malnutrition.	2005-07	15920769
Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver.	2005-07	15833929
Nrf2 as a novel molecular target for chemoprevention.	2005-06-28	15914268
Glutathione-mediated formation of oxygen free radicals by the major metabolite of oltipraz.	2005-06	15962931
Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression.	2005-05	15870285
Hepatic and intestinal first-pass effects of oltipraz in rats.	2005-05	15744718
Effect of enzyme inducers and inhibitors on the pharmacokinetics of oltipraz in rats.	2005-04	15831204
Safety and efficacy of weekly oral oltipraz in chronic smokers.	2005-04	15824161
Interspecies pharmacokinetic scaling of oltipraz in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics.	2005-04	15723427
Cancer chemopreventive oltipraz generates superoxide anion radical.	2005-03-01	15680910
Pharmacokinetics of oltipraz after intravenous and oral administration in rats with dehydration for 72 hours.	2005-03	15617135
Oltipraz regulates different categories of genes relevant to chemoprevention in human hepatocytes.	2005-02	15498785
Oltipraz, 3H-1,2-dithiole-3-thione, and sulforaphane induce overlapping and protective antioxidant responses in murine microglial cells.	2004-11-28	15454310
Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas.	2004-11	15508099
Dietary induction of NQO1 increases the antitumour activity of mitomycin C in human colon tumours in vivo.	2004-10-18	15467770
Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis.	2004-09-15	15374950
Ceramide, an apoptotic rheostat, inhibits CCAAT/enhancer binding protein-beta and NF-E2-related factor-2 activation: the role in glutathione S-transferase A2 gene repression.	2004-09	15319326
Effects of acute renal failure on the pharmacokinetics of oltipraz in rats.	2004-09	15295795
NF-kappaB activation by the chemopreventive dithiolethione oltipraz is exerted through stimulation of MEKK3 signaling.	2004-06-18	15047705
Prostate intraepithelial neoplasia in Noble rats, a potential intermediate endpoint for chemoprevention studies.	2004-06	15177500
Ceramide negatively regulates glutathione S-transferase gene transactivation via repression of hepatic nuclear factor-1 that is degraded by the ubiquitin proteasome system.	2004-06	15155840
Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.	2004-05-27	15161036
Pharmacokinetic changes of oltipraz after intravenous and oral administration to rats with liver cirrhosis induced by dimethylnitrosamine.	2004-05-04	15081153
Oltipraz inhibits inducible nitric oxide synthase in vitro and inhibits nitric oxide production in activated microglial cells.	2004-04-15	15047188
In vitro effect of low concentrations of oltipraz on the antioxidant defence of mouse hepatocytes and Schistosoma mansoni worms.	2004	15058738
Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action.	2004	14979919
Evaluation of the cancer chemopreventive potency of dithiolethione analogs of oltipraz.	2003-12	14555609
Oltipraz inhibits 3-methylcholanthrene induction of CYP1A1 by CCAAT/enhancer-binding protein activation.	2003-11-07	12941938
Phase 2 enzyme induction by the major metabolite of oltipraz.	2003-11	14615973
Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of constitutive androstane receptor.	2003-11	14570762
In vitro evaluation of chemopreventive agents using cultured human prostate epithelial cells.	2003-10-10	14534735
Pharmacokinetic interaction between oltipraz and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) after single intravenous and oral administration to rats.	2003-09	14604467
Induction of multidrug resistance protein 3 in rat liver is associated with altered vectorial excretion of acetaminophen metabolites.	2003-09	12920174
Oltipraz is a bifunctional inducer activating both phase I and phase II drug-metabolizing enzymes via the xenobiotic responsive element.	2003-08	12869639
Role of the AP-1 element and redox factor-1 (Ref-1) in mediating transcriptional induction of DT-diaphorase gene expression by oltipraz: a target for chemoprevention.	2003-07-01	12818361
Induction of NAD(P)H quinone: oxidoreductase1 inhibits carcinogen-induced aberrant crypt foci in colons of Sprague-Dawley rats.	2003-06	12815004
[Development of bladder cancer chemoprevention].	2003-03	12793013
Stability, blood partition and protein binding of an antifibrotic agent, oltipraz.	2001	12889516

Patents

Sample Use Guides

In Vivo Use Guide

Dose of either 90 or 120mg by mouth, tid

Route of Administration: Oral

In Vitro Use Guide

HEK293 and hPTCs were plated in a 96-well configuration. Cells were incubated overnight at 37◦C in a humidified incubator with an atmosphere of 5% CO2 prior to treatment. The cell treatments consisted of 1) 0.1% vehicle control (DMSO), 2) cisplatin at 0, 50,80 mkM doses, 3) Nrf2 activator [sulforaphane(5 mkM), oleanolic acid (5 mkM), or oltipraz (12 mkM)], or 4) cisplatin(at the above doses) combined with a Nrf2 activator at specified doses. Cells were incubated with Nrf2 activators for 12, 24, or 48 h beginning either 3 h prior to cisplatin or 3 h after initiation of cis-platin exposure. After the specified incubation time, MTT reagent(2 mg/mL) (Sigma Aldrich) in DMEM or EpiCM containing no FBS was added and cells were incubated for 4 h at 37◦C. MTT reagent was removed after the 4 h incubation period, MTT solubility solution (2% HCl, 25% H2O, 73% 2-propanol) was added and cell viability was analyzed at 550 nm by VersaMax microreader plate (MolecularDevices, Sunnyvale, CA).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:11:32 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:32 GMT 2025`
Record UNII	6N510JUL1Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NSC-347901

Preferred Name

English

OLTIPRAZ

Official Name

English

oltipraz [INN]

Common Name

English

4-METHYL-5-(PYRAZINYL)-3H-1,2-DITHIOLE-3-THIONE

Systematic Name

English

Oltipraz [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1742