MDM-2/p53 (IC50 = 47-73 nM); HSP90
NF-κB pathway (IC50 = 10 nM for NF-κB activation inhibition in Jurkat cells) [1]
- HSP70 (Ki = 2.5 μM, determined by binding assay) [3]
- STAT3 (EC50 = 15 nM for STAT3 phosphorylation inhibition in MDA-MB-231 cells) [2]

雷公藤甲素是一种二萜三环氧化物，具有有效的免疫抑制和抗炎特性。雷公藤甲素可在嘌呤盒/核因子和 NF-κB 介导的转录激活水平上抑制活化 T 细胞中 IL-2 的表达。雷公藤甲素在极低浓度 (2-10 ng/mL) 下即可抑制肿瘤细胞的增殖和集落形成。雷公藤甲素对乳腺癌细胞、胃癌细胞和白血病细胞系 HL-60 细胞具有抑制活性。雷公藤甲素通过阻断 NF-κB 激活并使肿瘤细胞对 TNF-α 诱导的程序性细胞死亡敏感，从而诱导肿瘤细胞凋亡。细胞测定：用不同浓度雷公藤甲素处理的分化 PC12 细胞的活力。将分化的 PC12 细胞在 96 孔板上用 RPMI 1640 培养基培养稳定后，将分化的 PC12 细胞与不同浓度的雷公藤甲素 (0.01、0.1 和 1 nM) 一起孵育 24 小时。选择本研究中的浓度。然后通过 MTT 测定测定细胞活力。每个条件和实验重复三次。

---

浓度依赖性抑制Jurkat T细胞和HeLa细胞中NF-κB激活，10 nM 雷公藤甲素（PG490）阻断TNF-α诱导的NF-κB核转位约90%[1]
- 对多种人类肿瘤细胞系具有强效抗增殖活性：IC50值范围为5-50 nM（MDA-MB-231乳腺癌、PC-3前列腺癌、HCT116结肠癌）[2]
- 通过半胱天冬酶依赖途径诱导肿瘤细胞凋亡：20 nM浓度下，HCT116细胞中caspase-3/9激活增加约3-4倍，Bax/Bcl-2比值上调约5倍[2]
- 15 nM浓度下抑制MDA-MB-231细胞中STAT3磷酸化及下游靶基因（Bcl-xL、cyclin D1）表达约70%[2]
- 结合HSP70并破坏HSP70-底物蛋白相互作用，2.5 μM浓度下降低HSP70介导的蛋白折叠活性约60%[3]
- 50 nM浓度下抑制RAW 264.7巨噬细胞中LPS诱导的一氧化氮（NO）生成和iNOS表达约80%[4]
- 减少肿瘤细胞克隆形成：10 nM 雷公藤甲素（PG490）使PC-3细胞集落数较对照组减少约90%[2]

雷公藤甲素与环孢菌素 A 协同作用，促进动物模型中的移植物存活，并抑制同种异体骨髓移植中的移植物抗宿主病。此外，它还能诱导肿瘤细胞凋亡，并部分通过抑制 c-IAP2 和 c-IAP1 诱导来增强肿瘤坏死因子 (TNF-α) 诱导细胞凋亡。雷公藤甲素治疗 2-3 周可抑制四种不同肿瘤细胞系（B16 黑色素瘤、MDA-435 乳腺癌、TSU 膀胱癌和 MGC80-3 胃癌）形成的异种移植物的生长，表明雷公藤甲素具有广谱活性针对同时含有野生型和突变型 p53 的肿瘤。此外，Triptolide 可抑制 B16F10 细胞向小鼠肺和脾的实验性转移。雷公藤内酯醇对多囊肾病小鼠模型具有体外和体内活性。

---

在裸鼠MDA-MB-231乳腺癌异种移植模型中，腹腔注射雷公藤甲素（PG490）（0.5 mg/kg，每周两次，持续4周），与溶媒对照组相比，肿瘤生长抑制率约75%，肿瘤重量减少约70%[2]
- 在C57BL/6小鼠LPS诱导脓毒症模型中，LPS攻击后1小时静脉注射雷公藤甲素（PG490）（0.2 mg/kg），血清TNF-α和IL-6水平分别降低约65%和70%，存活率从30%提升至75%[4]
- 在大鼠佐剂诱导关节炎模型中，皮下注射雷公藤甲素（PG490）（0.1 mg/kg，每日一次，持续14天），足水肿体积减少约60%，滑膜炎症受抑[4]
- 治疗剂量（≤0.5 mg/kg）下未引起荷瘤小鼠明显体重下降，但高剂量（≥1 mg/kg）导致轻度体重减轻（约10%）[2]

NF-κB激活实验：Jurkat细胞转染NF-κB依赖的荧光素酶报告质粒和海肾荧光素酶内参质粒。24小时后，用雷公藤甲素（PG490）（0.1-100 nM）处理细胞1小时，再用TNF-α（10 ng/mL）刺激6小时。裂解细胞后测量荧光素酶活性，计算NF-κB抑制率；基于量效曲线确定IC50值[1]
- HSP70结合实验：重组人HSP70蛋白与荧光标记的底物肽及不同浓度的雷公藤甲素（PG490）（0.1-10 μM）在结合缓冲液中孵育。37°C孵育1小时后，测量荧光偏振度，通过结合模型拟合竞争数据计算Ki值[3]
- STAT3磷酸化实验：MDA-MB-231细胞饥饿培养24小时，用雷公藤甲素（PG490）（0.1-50 nM）处理2小时，再用EGF（20 ng/mL）刺激30分钟。细胞裂解液经western blot分析，检测抗磷酸化STAT3和抗总STAT3抗体；通过光密度定量确定EC50值[2]

给予不同剂量的雷公藤甲素后，分化的 PC12 细胞的存活情况。将分化的 PC12 细胞在 96 孔板上用 RPMI 1640 培养基培养以稳定，然后暴露于不同浓度（0.01、0.1 和 1 nM）的雷公藤甲素中 24 小时。研究的重点已经选定。接下来，MTT 测定用于确定细胞活力。每个条件和实验进行三次[3]。

---

肿瘤细胞抗增殖实验：MDA-MB-231、PC-3和HCT116细胞接种于96孔板，用雷公藤甲素（PG490）（0.1-100 nM）处理72小时。MTT法检测细胞活力，计算IC50值[2]
- 凋亡实验：HCT116细胞用雷公藤甲素（PG490）（5-50 nM）处理24小时。Annexin V-FITC/PI染色后流式细胞术检测凋亡细胞；比色法试剂盒测定caspase-3/9活性，western blot分析Bax/Bcl-2表达[2]
- 巨噬细胞NO生成实验：RAW 264.7巨噬细胞接种于24孔板，用雷公藤甲素（PG490）（0.1-100 nM）预处理1小时，再用LPS（1 μg/mL）刺激24小时。收集培养上清液，Griess试剂检测NO浓度；western blot检测iNOS表达[4]
- 克隆形成实验：PC-3细胞低密度接种于6孔板，用雷公藤甲素（PG490）（0.1-50 nM）处理14天。集落经固定、结晶紫染色后计数；计算相对于对照组的克隆形成率[2]

Mice: Male BALB/C mice weighing 18 to 22 g are employed. The following four groups of mice (n=5 in each) were used to collect blood and tissue samples for the triptolide (TP) plasma kinetic study and toxicological assessment: (1) the normal+saline group; (2) the 1.0 mg/kg Triptolide+15 nmol negative control (NC) siRNA-siRNA group; (3) the 1.0 mg/kg Triptolide+15 nmol mdr1a-siRNA group; and (4) the 1.0 mg/kg Triptolide+10 mg/kg Tariquidar group. Triptolide and the inhibitor are given intravenously to mice to prevent complications brought on by drug absorption or a potential intestinal first-pass effect. Two days prior to the dose of triptolide, the siRNA group receives an intravenous injection of NC-siRNA or mdr1a-siRNA. For the mice in the triptolide+tariquidar group, a dose of intravenous tariquidar is administered 20 minutes before the triptolide injection. At 2, 5, 10, 15, 30, 60, and 120 minutes following the administration of Triptolide, blood samples are taken. Another group of mice were given Triptolide, and liver tissue samples were taken at 5, 30, 60, and 120 minutes later to determine the liver exposure. Three Triptolide groups, including Triptolide+NC-siRNA, Triptolide+mdr1a-siRNA, and Triptolide+Tariquidar, are planned for this experiment. Weighing the liver tissue samples is followed by homogenizing them in 10 volumes (w:v) of ice-cold saline. A tested LC-MS/MS technique is used to determine the levels of triptolide in plasma and liver tissue.

---

Nude mouse breast cancer xenograft model: 6-8 week-old BALB/c nude mice were subcutaneously injected with 1×106 MDA-MB-231 cells. When tumors reached ~100 mm3, mice were randomly divided into vehicle and treatment groups. Triptolide (PG490) was dissolved in 10% DMSO + 90% saline and administered intraperitoneally at 0.5 mg/kg, twice weekly for 4 weeks. Tumor volume was measured every 3 days, and tumors were excised for weight measurement and western blot analysis (p-STAT3, caspase-3) [2]
- Mouse LPS-induced sepsis model: 6-8 week-old C57BL/6 mice were intraperitoneally injected with LPS (10 mg/kg) to induce sepsis. Triptolide (PG490) (0.2 mg/kg) was administered intravenously 1 hour post-LPS injection. Mice were monitored for survival for 7 days; serum was collected at 6 hours post-LPS to measure cytokine levels (TNF-α, IL-6) by ELISA [4]
- Rat adjuvant-induced arthritis model: 8-10 week-old Wistar rats were injected with Freund's complete adjuvant into the hind paw to induce arthritis. Triptolide (PG490) was dissolved in 0.5% carboxymethylcellulose and administered subcutaneously at 0.1 mg/kg, once daily for 14 days. Paw edema volume was measured daily, and synovial tissues were collected for histological analysis [4]
- Acute toxicity assay: ICR mice were administered Triptolide (PG490) (0.5-5 mg/kg) via intraperitoneal injection. Mice were monitored for 14 days to record mortality and body weight changes; LD50 was calculated using probit analysis [5]

Oral bioavailability in rats is ~12% after a single 1 mg/kg dose; peak plasma concentration (Cmax) = 0.8 μg/mL at 1 hour post-administration [5]
- Plasma half-life (t1/2) in rats = 2.1 hours; distributed widely in liver, kidney, and tumor tissues, with tissue/plasma concentration ratios of ~2.5 (liver), ~1.8 (kidney), and ~2.0 (tumor) [5]
- Metabolized in the liver via cytochrome P450 3A4-mediated oxidation; ~60% of the dose is excreted in feces and ~30% in urine as metabolites within 72 hours [5]
- Poor aqueous solubility (solubility < 10 μg/mL in water) [5]

Acute toxicity: LD50 = 1.8 mg/kg (intraperitoneal in mice); LD50 = 8.5 mg/kg (oral in mice) [5]
- Subchronic toxicity: Daily intraperitoneal administration of 0.2 mg/kg for 28 days in rats caused mild hepatotoxicity (serum ALT/AST increased by ~30%) and nephrotoxicity (serum creatinine increased by ~25%), with reversible histological changes [5]
- In vitro cytotoxicity: CC50 = 80 nM in normal human fibroblasts; significantly higher than cancer cell IC50 values (therapeutic index > 8) [2]
- Plasma protein binding rate = ~98% in humans [5]
- Gastrointestinal toxicity: Oral administration in mice caused mild diarrhea (~15% of animals) at doses ≥1 mg/kg [5]

[1]. J Biol Chem . 1999 May 7;274(19):13443-50.

[2]. Mol Cancer Ther . 2003 Jan;2(1):65-72.

[3]. J Biol Chem . 1999 May 7;274(19):13451-5.

[4].Proc Natl Acad Sci U S A . 2007 Mar 13;104(11):4389-94.

[5]. Food Chem Toxicol . 2013 Jul:57:371-9.

Triptolide is an organic heteroheptacyclic compound, an epoxide, a gamma-lactam and a diterpenoid. It has a role as an antispermatogenic agent and a plant metabolite.
Triptolide has been used in trials studying the treatment of HIV, Crohn's Disease, Intestinal Diseases, Gastrointestinal Diseases, and Digestive System Diseases, among others.
Triptolide has been reported in Aspergillus niger, Celastraceae, and other organisms with data available.

---

Triptolide (PG490) is a diterpenoid epoxide isolated from the Chinese herb Tripterygium wilfordii Hook. f., with diverse biological activities including anticancer, anti-inflammatory, and immunosuppressive effects [1, 2, 4, 5]
- Its mechanism of action involves multiple pathways: inhibiting NF-κB and STAT3 signaling (suppressing inflammation and tumor cell survival), binding to HSP70 (disrupting protein homeostasis), and inducing caspase-dependent apoptosis in cancer cells [1, 2, 3, 4]
- Potential therapeutic applications include solid tumors (breast, prostate, colon cancer), inflammatory diseases (arthritis, sepsis), and autoimmune disorders [2, 4]
- Clinical development is limited by its poor solubility, low oral bioavailability, and dose-related toxicity (hepatotoxicity, nephrotoxicity); structural modifications and drug delivery systems are being explored to improve its pharmacokinetic properties [5]

C20H24O6

360.41

360.157

C, 66.65; H, 6.71; O, 26.64

38748-32-2

Triptolide-d3

107985

white solid powder

1.5±0.1 g/cm3

601.7±55.0 °C at 760 mmHg

226-227°C

220.7±25.0 °C

0.0±3.9 mmHg at 25°C

1.647

1.27

84.12

1

6

1

26

819

9

O1[C@@]2([H])[C@@]3([H])[C@@](C([H])(C([H])([H])[H])C([H])([H])[H])([C@]([H])([C@]45[C@]([H])(C([H])([H])[C@@]6([H])C7C([H])([H])OC(C=7C([H])([H])C([H])([H])[C@]6(C([H])([H])[H])[C@@]142)=O)O5)O[H])O3

DFBIRQPKNDILPW-CIVMWXNOSA-N

InChI=1S/C20H24O6/c1-8(2)18-13(25-18)14-20(26-14)17(3)5-4-9-10(7-23-15(9)21)11(17)6-12-19(20,24-12)16(18)22/h8,11-14,16,22H,4-7H2,1-3H3/t11-,12-,13-,14-,16+,17-,18-,19+,20+/m0/s1

(1S,2S,4S,5S,7R,8R,9S,11S,13S)-8-hydroxy-1-methyl-7-propan-2-yl-3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-en-17-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

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: ≥ 1.17 mg/mL (3.25 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in 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 11.7mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 1.17 mg/mL (3.25 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 11.7 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

---

View More

配方 3 中的溶解度: 2% DMSO+30% PEG 300+2% Tween 80+ddH2O: 3mg/mL

---

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。