CAS 64224-21-1|Oltipraz

Introduction：Basic information about CAS 64224-21-1|Oltipraz, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Oltipraz BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles35
8. Synonyms

Common Name	Oltipraz
CAS Number	64224-21-1	Molecular Weight	226.342
Density	1.5±0.1 g/cm3	Boiling Point	408.1±55.0 °C at 760 mmHg
Molecular Formula	C₈H₆N₂S₃	Melting Point	165-166ºC
MSDS	ChineseUSA	Flash Point	200.6±31.5 °C
Symbol	GHS07	Signal Word	Warning

Names

Name	oltipraz
Synonym	More Synonyms

Oltipraz BiologicalActivity

Description	Oltipraz has an inhibitory effect on HIF-1α activation by insulin in a time-dependent manner, completely abrogating HIF-1α induction at ≥10 μM concentrations, the IC50 of Oltipraz for HIF-1α inhibition is 10 μM.IC50 value: 10 μMTarget: HIF-1αin vitro: Oltipraz inhibits HIF-1α activity and HIF-1α-dependent tumor growth, which may result from a decrease in HIF-1α stability through S6K1 inhibition in combination with an H2O2-scavenging effect. Oltipraz treatment also inhibits HIF-1α activation stimulated by either hypoxia or CoCl2. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth. [1] Oltipraz is also a competitive inhibitor of this cytochrome P450, with an apparent Ki of 10 μM. [2]in vivo: In wild-type mice, hepatic levels of mRNA for all of the genes analyzed were significantly increased after Oltipraz treatment, with the highest increase (treated/control) for NQO1 mRNA levels (7.6-fold). The Northern blot analyses demonstrated that the observed increases in GST and NQO1 activities by Oltipraz in wild-type mice were preceded by significant elevations in RNA expression. Interestingly, mRNA levels of Nrf2 itself were increased more than 3-fold by Oltipraz treatment. [2]
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>HIF/HIF Prolyl-HydroxylaseResearch Areas >>Cancer
References	[1]. Lee WH, et al. Oltipraz and dithiolethione congeners inhibit hypoxia-inducible factor-1alpha activity through p70 ribosomal S6 kinase-1 inhibition and H2O2-scavenging effect. Mol Cancer Ther. 2009 Oct;8(10):2791-802. [2]. Ramos-Gomez M, et al. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3410-5. [3]. Lv S, et al. Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism. J Endocrinol. 2017 Aug;234(2):73-87.

Description

Oltipraz has an inhibitory effect on HIF-1α activation by insulin in a time-dependent manner, completely abrogating HIF-1α induction at ≥10 μM concentrations, the IC50 of Oltipraz for HIF-1α inhibition is 10 μM.IC50 value: 10 μMTarget: HIF-1αin vitro: Oltipraz inhibits HIF-1α activity and HIF-1α-dependent tumor growth, which may result from a decrease in HIF-1α stability through S6K1 inhibition in combination with an H2O2-scavenging effect. Oltipraz treatment also inhibits HIF-1α activation stimulated by either hypoxia or CoCl2. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth. [1] Oltipraz is also a competitive inhibitor of this cytochrome P450, with an apparent Ki of 10 μM. [2]in vivo: In wild-type mice, hepatic levels of mRNA for all of the genes analyzed were significantly increased after Oltipraz treatment, with the highest increase (treated/control) for NQO1 mRNA levels (7.6-fold). The Northern blot analyses demonstrated that the observed increases in GST and NQO1 activities by Oltipraz in wild-type mice were preceded by significant elevations in RNA expression. Interestingly, mRNA levels of Nrf2 itself were increased more than 3-fold by Oltipraz treatment. [2]

Related Catalog

Signaling Pathways >>Metabolic Enzyme/Protease >>HIF/HIF Prolyl-HydroxylaseResearch Areas >>Cancer

References

[1]. Lee WH, et al. Oltipraz and dithiolethione congeners inhibit hypoxia-inducible factor-1alpha activity through p70 ribosomal S6 kinase-1 inhibition and H2O2-scavenging effect. Mol Cancer Ther. 2009 Oct;8(10):2791-802.

[2]. Ramos-Gomez M, et al. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3410-5.

[3]. Lv S, et al. Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism. J Endocrinol. 2017 Aug;234(2):73-87.

Chemical & Physical Properties

Density	1.5±0.1 g/cm3
Boiling Point	408.1±55.0 °C at 760 mmHg
Melting Point	165-166ºC
Molecular Formula	C₈H₆N₂S₃
Molecular Weight	226.342
Flash Point	200.6±31.5 °C
Exact Mass	225.969315
PSA	114.35000
LogP	1.92
Vapour Pressure	0.0±0.9 mmHg at 25°C
Index of Refraction	1.760
InChIKey	CKNAQFVBEHDJQV-UHFFFAOYSA-N
SMILES	Cc1c(-c2cnccn2)ssc1=S
Storage condition	2-8°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JP1293000

CHEMICAL NAME :: 3H-1,2-Dithiole-3-thione, 4-methyl-5-pyrazinyl-

CAS REGISTRY NUMBER :: 64224-21-1

LAST UPDATED :: 199706

DATA ITEMS CITED :: 9

MOLECULAR FORMULA :: C8-H6-N2-S3

MOLECULAR WEIGHT :: 226.34

WISWESSER LINE NOTATION :: T6N DNJ B- ET5SSYJ CUS D1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 43 mg/kg/D

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >50 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: >100 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 10920 mg/kg/1Y-I

TOXIC EFFECTS :: Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 9100 mg/kg/13W-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 21840 mg/kg/1Y-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Rodent - hamster Lung

DOSE/DURATION :: 1 mg/L

REFERENCE :: CBTOE2 Cell Biology and Toxicology. (Princeton Scientific Pub., Inc., 301 N. Harrison St., CN 5279, Princeton, NJ 08540) V.1- 1984- Volume(issue)/page/year: 2,379,1986

Safety Information

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H315-H319-H335
Precautionary Statements	P261-P305 + P351 + P338
Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Gloves
Risk Phrases	R36/37/38
Safety Phrases	26-36/37/39
RIDADR	NONH for all modes of transport
RTECS	JP1293000
HS Code	2933990090

Customs

HS Code	2933990090
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles35

Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

Diabetes 63(10) , 3483-96, (2014)

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) ge...

Antioxidant and mitochondrial protective effects of oxidized metabolites of oltipraz.

Expert Opin. Drug Metab. Toxicol. 6(2) , 213-24, (2010)

Comprehensive studies indicate that oltipraz exerts cancer chemopreventive effects. Oltipraz has other therapeutic potentials, which include anti-fibrotic effect, inhibition of insulin resistance, mit...

Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats.

Oncol. Rep. 21(6) , 1559-65, (2009)

Inducers of phase II detoxifying enzymes have been studied as chemopreventive agents for a variety of cancers. Phase II detoxifying enzymes may play a significant role in preventing carcinogen-induced...

Synonyms

Oltipraz

4-methyl-5-pyrazin-2-yldithiole-3-thione

RP-35,972

4-Methyl-5-(pyrazin-2-yl)-3H-1,2-dithiole-3-thione

4-Methyl-5-(2-pyrazinyl)-3H-1,2-dithiole-3-thione

4-Methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione

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

4-Methyl-5-pyrazin-2-yl-1,2-dithiole-3-thione

3H-1,2-Dithiole-3-thione, 4-methyl-5-(2-pyrazinyl)-

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