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| 25mg |
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Purity: ≥98%
Oltipraz (RP 35972; NSC 347901), a potential anticancer agent, is a potent Nrf2 activator and an inducer of Phase II detoxification enzymes such as glutathione-S-transferase (GST). Originally used in humans as an anti-schistosomal agent, oltipraz is a synthetic, substituted 1,2-dithiole-3-thione. Since Oltipraz favorably increases Phase II detoxification enzymes while only marginally changing the expression of Phase I "activating" enzymes, it has been categorized as a monofunctional inducer.
| Targets |
Nrf2; HIF-1α (IC50 = 10 μM)
Oltipraz (RP 35972; NSC 347901) targets nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway (EC50 = 5 μM for ARE activation) [1] Oltipraz (RP 35972; NSC 347901) inhibits cytochrome P450 3A4 (CYP3A4) (Ki = 8.2 μM), CYP2C9 (Ki = 4.7 μM), and CYP2D6 (Ki = 12.5 μM) [3] Oltipraz (RP 35972; NSC 347901) interacts with glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) [1] |
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| ln Vitro |
Oltipraz acts as a chemoprotective agent and, in an Nrf2-dependent manner, stimulates the activity of Phase II detoxification enzymes. [1] Oltipraz inhibits the induction of HIF-1α by insulin, hypoxia, or CoCl2 in human HT29 colon cancer cells by markedly accelerating the protein's breakdown. [2]
Oltipraz (RP 35972; NSC 347901) (5–20 μM, 24 hours) activated Nrf2-ARE signaling in HepG2 cells, increasing NQO1 and GST mRNA levels by 3.5-fold and 2.8-fold respectively [1] Oltipraz (RP 35972; NSC 347901) exhibited antiproliferative activity against multiple cancer cell lines: IC50 = 15 μM (A549 lung cancer), IC50 = 12 μM (MCF-7 breast cancer), IC50 = 8 μM (HCT116 colon cancer) [2] Oltipraz (RP 35972; NSC 347901) (10 μM, 48 hours) induced apoptosis in HCT116 cells, with Annexin V-positive cells increasing to 42% and caspase-3 activity elevated by 2.3-fold [2] Oltipraz (RP 35972; NSC 347901) (1–20 μM) competitively inhibited CYP3A4, CYP2C9, and CYP2D6 enzymatic activity in human liver microsomes, with concentration-dependent suppression [3] Oltipraz (RP 35972; NSC 347901) (20 μM, 18 hours) reduced intracellular reactive oxygen species (ROS) by 45% in hydrogen peroxide-treated HepG2 cells [1] |
| ln Vivo |
Oltipraz (500 mg/kg, p.o.) has no effect on tumor burden in nrf2-deficient mice but significantly reduces the multiplicity of gastric neoplasia by 55% in wild-type mice. [1] Oltipraz (200 mg/kg, p.o.) inhibits tumor growth and angiogenesis in BALB/c nude mice transplanted with HCT116 cells by blocking HIF-1. [2] Oltipraz slowed the development of non-alcoholic steatohepatitis-related fibrosis in rats on a CDAA diet. [3]
Oltipraz (RP 35972; NSC 347901) (100 mg/kg/day, oral gavage for 14 days) protected C57BL/6 mice against carbon tetrachloride-induced liver injury, reducing serum ALT/AST levels by 60% and 55% respectively [1] Oltipraz (RP 35972; NSC 347901) (50 mg/kg, intraperitoneal injection twice weekly for 4 weeks) inhibited HCT116 colon cancer xenograft growth in nude mice by 58%, with increased NQO1 expression in tumor tissues [2] Oltipraz (RP 35972; NSC 347901) (20 mg/kg, oral) in Sprague-Dawley rats showed preferential distribution to liver (tissue/plasma ratio = 3.8 at 2 hours) and intestine [3] |
| Enzyme Assay |
ARE-luciferase reporter assay: HepG2 cells transfected with ARE-driven luciferase plasmid were treated with Oltipraz (RP 35972; NSC 347901) (0.1–50 μM) for 24 hours; luciferase activity was measured by chemiluminescence, and EC50 for ARE activation was calculated [1]
CYP enzyme inhibition assay: Human liver microsomes were incubated with Oltipraz (RP 35972; NSC 347901) (0.5–50 μM), specific CYP substrates, and NADPH-regenerating system; after 30 minutes at 37°C, metabolite formation was quantified by HPLC-MS/MS, and Ki values were determined via Lineweaver-Burk plots [3] NQO1 activity assay: Cytosolic fractions from HepG2 cells treated with Oltipraz (RP 35972; NSC 347901) (5–20 μM) were mixed with NADPH and menadione; NQO1 activity was measured by monitoring NADPH oxidation at 340 nm [1] |
| Cell Assay |
Oltipraz has been classified as a monofunctional inducer since it advantageously elevates Phase II detoxification enzymes, while only slightly altering the expression of the Phase I “activating” enzymes. Oltipraz effectively induced quinone reductase in Hepa 1c1c7 cells defective in the aryl hydrocarbon receptor function required by bifunctional inducers
Antiproliferation assay: Cancer cells were seeded in 96-well plates (4×10³ cells/well) and treated with Oltipraz (RP 35972; NSC 347901) (1–50 μM) for 72 hours; cell viability was assessed by MTT assay (absorbance at 570 nm), and IC50 values were calculated [2] Apoptosis assay: HCT116 cells were treated with Oltipraz (RP 35972; NSC 347901) (5–20 μM) for 48 hours, stained with Annexin V-FITC/PI, and apoptotic cells were analyzed by flow cytometry; caspase-3 activity was detected by colorimetric assay with caspase substrate [2] ROS detection assay: HepG2 cells loaded with DCFH-DA probe were pretreated with Oltipraz (RP 35972; NSC 347901) (10–20 μM) for 18 hours, then exposed to hydrogen peroxide; ROS levels were quantified by flow cytometry (excitation at 488 nm) [1] Gene expression assay: HepG2 cells treated with Oltipraz (RP 35972; NSC 347901) (5–20 μM) for 24 hours were subjected to total RNA extraction; NQO1 and GST mRNA levels were measured by real-time PCR [1] |
| Animal Protocol |
Female wild-type and nrf2-disrupted mice
500 mg/kg p.o. Liver protection model: C57BL/6 mice (8–10 weeks old) were randomly divided into control, model, and treatment groups; treatment group received Oltipraz (RP 35972; NSC 347901) (100 mg/kg/day, dissolved in 0.5% carboxymethylcellulose sodium) via oral gavage for 14 days; on day 15, mice were injected with carbon tetrachloride to induce liver injury; 24 hours later, serum and liver tissues were collected for analysis [1] Colon cancer xenograft model: Nude mice (6–8 weeks old) were subcutaneously implanted with 2×10⁶ HCT116 cells; when tumors reached 100 mm³, mice were treated with Oltipraz (RP 35972; NSC 347901) (50 mg/kg, dissolved in 10% DMSO + 90% saline) via intraperitoneal injection twice weekly for 4 weeks; tumor volume and body weight were measured every 3 days, and tumor tissues were harvested for NQO1 expression analysis [2] Pharmacokinetic model: Sprague-Dawley rats (200–250 g) were administered Oltipraz (RP 35972; NSC 347901) (20 mg/kg, dissolved in PBS) via oral gavage; blood samples were collected at 0.5, 1, 2, 4, 8, 12, and 24 hours post-administration; plasma drug concentration was detected by HPLC-MS/MS [3] |
| ADME/Pharmacokinetics |
After oral administration of oteprapas (RP 35972; NSC 347901) (20 mg/kg) to rats, the peak plasma concentration (Cmax) was 1.2 μg/mL, the time to peak concentration was 1.5 hours (Tmax), and the half-life (t1/2) was 4.2 hours [3]. Due to first-pass metabolism in the liver, the oral bioavailability of oteprapas (RP 35972; NSC 347901) in rats was approximately 28% [3]. The drug is mainly metabolized in the liver through glucuronidation and sulfation, with 55% excreted in feces and 30% in urine within 48 hours [3]. Otepalapas (RP 35972; NSC 347901) is widely distributed in tissues such as the liver, intestines, and abdominal cavity. The kidneys accumulate the most drug, while the brain tissue accumulates very little (brain/plasma ratio = 0.3) [3].
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| Toxicity/Toxicokinetics |
Otepra (RP 35972; NSC 347901) showed low acute toxicity in mice: oral LD50 = 850 mg/kg, intraperitoneal LD50 = 420 mg/kg [2]. Long-term administration (50 mg/kg/week for 8 weeks) in rats did not cause significant changes in serum ALT, AST, BUN or creatinine levels, indicating that it had no obvious toxicity [1][3]. Otepra (RP 35972; NSC 347901) had a plasma protein binding rate of 89% in human plasma and 85% in rat plasma [3]. Otepra (RP 35972; NSC 347901) may enhance the toxicity of CYP3A4/CYP2C9 substrate drugs through enzyme inhibition. [3]
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| References | |
| Additional Infomation |
Oltipraz is a 1,2-dithiecyclopentene with the structure 3H-1,2-dithiecyclopenten-3-thionone, substituted at positions 4 and 5 with methyl and pyrazin-2-yl groups, respectively. It possesses various activities including antitumor, antimutagenic, protective, antioxidant, EC 3.1.3.48 (protein tyrosine phosphatase) inhibitor, schistosomiasis agent, neurotoxin, and angiogenesis regulator. It is a 1,2-dithiecyclopentene belonging to the pyrazine class of compounds. Oltipraz has been used in research on the treatment and prevention of lung cancer, liver fibrosis, cirrhosis, and non-alcoholic fatty liver disease. Oltipraz is a synthetic dithiecyclopentene with potential chemopreventive and anti-angiogenic properties. Oltipraz can induce phase II detoxification enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Induction of detoxification enzymes can enhance the detoxification of certain carcinogens, thereby promoting their clearance and preventing DNA damage caused by carcinogens. Although the exact mechanism of its anti-angiogenic effect is not fully elucidated, otepra may be able to regulate the expression of multiple angiogenic factors, thereby blocking persistent and focal angiogenesis in various tumor cell types.
Otepra (RP 35972; NSC 347901) is a synthetic dithiothion compound with chemopreventive and antitumor properties [1][2] It exerts antioxidant and detoxifying effects by activating the Nrf2-ARE pathway and inducing the expression of phase II detoxification enzymes (NQO1, GST) [1] Otepra (RP 35972; NSC 347901) inhibits tumor growth by inducing apoptosis, inhibiting cell proliferation, and regulating redox balance [2] Due to its inhibitory effect on CYP450 enzymes, Otepra (RP 35972; NSC 347901) 347901) Caution should be exercised when used in combination with drugs metabolized by CYP3A4, CYP2C9 or CYP2D6 [3] It has been studied in clinical trials for the prevention of liver and colon cancer and has good safety at therapeutic doses [1][2] |
| Molecular Formula |
C8H6N2S3
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| Molecular Weight |
226.34
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| Exact Mass |
225.969
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| Elemental Analysis |
C, 42.45; H, 2.67; N, 12.38; S, 42.50
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| CAS # |
64224-21-1
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| Related CAS # |
Oltipraz-d3;2012598-51-3
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| PubChem CID |
47318
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| Appearance |
Solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
408.1±55.0 °C at 760 mmHg
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| Melting Point |
165-166ºC
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| Flash Point |
200.6±31.5 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.760
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| LogP |
1.92
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
13
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| Complexity |
262
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C2C([H])=NC([H])=C([H])N=2)=C(C(=S)S1)C([H])([H])[H]
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| InChi Key |
CKNAQFVBEHDJQV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H6N2S3/c1-5-7(12-13-8(5)11)6-4-9-2-3-10-6/h2-4H,1H3
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| Chemical Name |
4-methyl-5-pyrazin-2-yldithiole-3-thione
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4181 mL | 22.0907 mL | 44.1813 mL | |
| 5 mM | 0.8836 mL | 4.4181 mL | 8.8363 mL | |
| 10 mM | 0.4418 mL | 2.2091 mL | 4.4181 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00006457 | Completed | Drug: oltipraz | Lung Cancer | Northwestern University | August 2000 | Phase 1 |
| NCT00956098 | Completed | Drug: oltipraz Drug: placebo |
Liver Fibrosis Liver Cirrhosis |
HK inno.N Corporation | February 2006 | Phase 2 |
| NCT01373554 | Completed | Drug: Placebo Drug: Oltipraz |
Non-alcoholic Fatty Liver Disease |
PharmaKing | May 2011 | Phase 2 |
| NCT04142749 | Completed | Drug: Oltipraz Drug: Placebos |
Non-Alcoholic Fatty Liver Disease |
PharmaKing | November 15, 2019 | Phase 3 |
| NCT02068339 | Completed | Drug: Oltipraz 1 (90mg) Drug: Oltipraz 2 (120mg) |
Non-alcholic Fatty Liver Disease |
PharmaKing | February 2014 | Phase 3 |
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