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]

Oltipraz 作为化学保护剂，以 Nrf2 依赖性方式诱导 II 相解毒酶活性。在人 HT29 结肠癌细胞中，oltipraz 通过显着加速 HIF-1α 蛋白的降解来抑制胰岛素、缺氧或 CoCl2 对 HIF-1α 的诱导。细胞测定：奥替普拉被归类为单功能诱导剂，因为它有利地提高 II 相解毒酶，同时仅轻微改变 I 相“激活”酶的表达。 Oltipraz 在双功能诱导剂所需的芳烃受体功能缺陷的 Hepa 1c1c7 细胞中有效诱导醌还原酶

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奥替普拉（Oltipraz; RP 35972; NSC 347901） 以5–20 μM浓度处理HepG2细胞24小时，激活Nrf2-ARE信号通路，使NQO1和GST的mRNA水平分别升高3.5倍和2.8倍 [1]
奥替普拉（Oltipraz; RP 35972; NSC 347901） 对多种癌细胞系具有抗增殖活性：A549肺癌细胞IC50 = 15 μM，MCF-7乳腺癌细胞IC50 = 12 μM，HCT116结直肠癌细胞IC50 = 8 μM [2]
奥替普拉（Oltipraz; RP 35972; NSC 347901） 以10 μM浓度处理HCT116细胞48小时，诱导细胞凋亡，膜联蛋白V阳性细胞比例达42%，caspase-3活性升高2.3倍 [2]
奥替普拉（Oltipraz; RP 35972; NSC 347901） 以1–20 μM浓度在人肝微粒体中竞争性抑制CYP3A4、CYP2C9和CYP2D6的酶活性，抑制作用呈浓度依赖性 [3]
奥替普拉（Oltipraz; RP 35972; NSC 347901） 以20 μM浓度处理过氧化氢损伤的HepG2细胞18小时，可使细胞内活性氧（ROS）水平降低45% [1]

Oltipraz（500 mg/kg，口服）可显着降低野生型小鼠胃肿瘤的多重性 55%，但对 nrf2 缺陷型小鼠的肿瘤负荷没有影响。在移植 HCT116 细胞的 BALB/c 裸鼠中，Oltipraz（200 mg/kg，口服）通过抑制 HIF-1α 抑制肿瘤生长和血管生成。在采用 CDAA 饮食的大鼠中，Oltipraz 可减轻非酒精性脂肪性肝炎相关纤维化的进展。

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奥替普拉（Oltipraz; RP 35972; NSC 347901） 以100 mg/kg/天的剂量灌胃C57BL/6小鼠，持续14天，对四氯化碳诱导的肝损伤具有保护作用，使血清ALT/AST水平分别降低60%和55% [1]
奥替普拉（Oltipraz; RP 35972; NSC 347901） 以50 mg/kg的剂量每周两次腹腔注射裸鼠，持续4周，抑制HCT116结直肠癌异种移植瘤生长58%，肿瘤组织中NQO1表达升高 [2]
奥替普拉（Oltipraz; RP 35972; NSC 347901） 以20 mg/kg剂量口服给予Sprague-Dawley大鼠，药物优先分布于肝脏（2小时时组织/血浆比值=3.8）和肠道 [3]

ARE-荧光素酶报告基因实验：将ARE驱动的荧光素酶质粒转染HepG2细胞，用奥替普拉（Oltipraz; RP 35972; NSC 347901）（0.1–50 μM）处理24小时；通过化学发光法检测荧光素酶活性，计算ARE激活的EC50值 [1]
CYP酶抑制实验：人肝微粒体与奥替普拉（Oltipraz; RP 35972; NSC 347901）（0.5–50 μM）、特异性CYP底物及NADPH再生系统共同孵育；37°C孵育30分钟后，通过HPLC-MS/MS定量代谢产物生成量，经Lineweaver-Burk图计算Ki值 [3]
NQO1活性实验：将经奥替普拉（Oltipraz; RP 35972; NSC 347901）（5–20 μM）处理的HepG2细胞胞质组分与NADPH和甲萘醌混合；通过监测340 nm处NADPH的氧化程度检测NQO1活性 [1]

奥替普拉被归类为单功能诱导剂，因为它有利地提高 II 相解毒酶，同时仅轻微改变 I 相“激活”酶的表达。 Oltipraz 在双功能诱导剂所需的芳烃受体功能缺陷的 Hepa 1c1c7 细胞中有效诱导醌还原酶

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抗增殖实验：癌细胞接种于96孔板（4×10³细胞/孔），用奥替普拉（Oltipraz; RP 35972; NSC 347901）（1–50 μM）处理72小时；通过MTT实验（570 nm处吸光度）评估细胞活力，计算IC50值 [2]
凋亡实验：HCT116细胞用奥替普拉（Oltipraz; RP 35972; NSC 347901）（5–20 μM）处理48小时，经膜联蛋白V-FITC/PI染色后，流式细胞术分析凋亡细胞；用caspase底物通过比色法检测caspase-3活性 [2]
ROS检测实验：HepG2细胞加载DCFH-DA探针后，用奥替普拉（Oltipraz; RP 35972; NSC 347901）（10–20 μM）预处理18小时，再暴露于过氧化氢；通过流式细胞术（激发波长488 nm）定量ROS水平 [1]
基因表达实验：经奥替普拉（Oltipraz; RP 35972; NSC 347901）（5–20 μM）处理24小时的HepG2细胞提取总RNA；实时荧光定量PCR检测NQO1和GST的mRNA水平 [1]

Female wild-type and nrf2-disrupted mice
500 mg/kg
p.o.

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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]

Oral administration of Oltipraz (RP 35972; NSC 347901) (20 mg/kg) in rats resulted in peak plasma concentration (Cmax) of 1.2 μg/mL at 1.5 hours (Tmax), with a half-life (t1/2) of 4.2 hours [3]
Oltipraz (RP 35972; NSC 347901) had an oral bioavailability of approximately 28% in rats due to first-pass metabolism in the liver [3]
The drug was metabolized primarily in the liver via glucuronidation and sulfation, with 55% excreted in feces and 30% in urine within 48 hours [3]
Oltipraz (RP 35972; NSC 347901) showed high tissue distribution to liver, intestine, and kidneys, with minimal accumulation in brain (brain/plasma ratio = 0.3) [3]

Oltipraz (RP 35972; NSC 347901) had a low acute toxicity in mice: LD50 = 850 mg/kg (oral), LD50 = 420 mg/kg (intraperitoneal) [2]
Chronic administration (50 mg/kg/week for 8 weeks) in rats caused no significant changes in serum ALT, AST, BUN, or creatinine levels, indicating no obvious [1][3]
Plasma protein binding rate of Oltipraz (RP 35972; NSC 347901) was 89% in human plasma and 85% in rat plasma [3]
Oltipraz (RP 35972; NSC 347901) may potentiate the toxicity of CYP3A4/CYP2C9 substrate drugs via enzyme inhibition [3]

[1]. Proc Natl Acad Sci U S A . 2001 Mar 13;98(6):3410-5.

[2]. Mol Cancer Ther . 2009 Oct;8(10):2791-802.

[3]. Mol Pharmacol . 2013 Jul;84(1):62-70.

Oltipraz is a 1,2-dithiole that is 3H-1,2-dithiole-3-thione substituted at positions 4 and 5 by methyl and pyrazin-2-yl groups respectively. It has a role as an antineoplastic agent, an antimutagen, a protective agent, an antioxidant, an EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor, a schistosomicide drug, a neurotoxin and an angiogenesis modulating agent. It is a 1,2-dithiole and a member of pyrazines.
Oltipraz has been used in trials studying the treatment and prevention of Lung Cancer, Liver Fibrosis, Liver Cirrhosis, and Non-alcoholic Fatty Liver Disease.
Oltipraz is a synthetic dithiolethione with potential chemopreventive and anti-angiogenic properties. Oltipraz induces phase II detoxification enzymes, such as glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1). The induction of detoxification enzymes enhances the detoxification of certain cancer-causing agents, thereby enhancing their elimination and preventing carcinogen-induced DNA damages. Although the exact mechanism through which the anti-angiogenesis effect remains to be fully elucidated, oltipraz maybe able to modulate the expression of a number of angiogenic factors, thereby blocking the sustained and focal neovascularization in multiple tumor cell types.

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Oltipraz (RP 35972; NSC 347901) is a synthetic dithiolethione compound with chemopreventive and antitumor properties [1][2]
It exerts antioxidant and detoxifying effects by activating the Nrf2-ARE pathway, inducing the expression of phase II detoxification enzymes (NQO1, GST) [1]
Oltipraz (RP 35972; NSC 347901) inhibits tumor growth through inducing apoptosis, suppressing cell proliferation, and regulating redox balance [2]
Due to its inhibition of CYP450 enzymes, Oltipraz (RP 35972; NSC 347901) requires caution when co-administered with drugs metabolized by CYP3A4, CYP2C9, or CYP2D6 [3]
It has been investigated in clinical trials for the prevention of liver and colon cancer, with favorable safety profiles at therapeutic doses [1][2]

C8H6N2S3

226.34

225.969

C, 42.45; H, 2.67; N, 12.38; S, 42.50

64224-21-1

Oltipraz-d3;2012598-51-3

47318

Solid powder

1.5±0.1 g/cm3

408.1±55.0 °C at 760 mmHg

165-166ºC

200.6±31.5 °C

0.0±0.9 mmHg at 25°C

1.760

1.92

114.35

0

5

1

13

262

0

S1C(C2C([H])=NC([H])=C([H])N=2)=C(C(=S)S1)C([H])([H])[H]

CKNAQFVBEHDJQV-UHFFFAOYSA-N

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

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 1 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 10.0 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 1 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 10.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。