Oltipraz

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]

Signaling Pathways >> Metabolic Enzyme/Protease >> HIF/HIF Prolyl-Hydroxylase

Research Areas >> Cancer

[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.

Dimethyloxalylglycine | PT-2385 | FG-4592 | PX-478 2HCl | BAY 87-2243 | Vadadustat | Daprodustat | Chlorogenic acid | LW 6 | Molidustat | IOX2 | Paeoniflorin | KC7F2 | oroxylin A | JNJ-42041935

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