Minnelide
(Synonyms: 明奈利德) 目录号 : GC36612
Minnelide 是雷公藤内酯的衍生物，在许多肿瘤类型 (特别是在胰腺癌) 中显示出抗肿瘤 (antitumor) 活性。 Minnelide 可导致凋亡 (apoptotic)。
Cas No.:1254702-87-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Minnelide is a prodrug of triptolide that shows potent antitumor activity in a number of tumor types, particularly in pancreatic cancer. Minnelide causes apoptotic[1].
Minnelide (0-200 nM; 48 hours) shows significantly decreased cell viability in pancreatic cancer cell lines after treatment in the presence, but not in the absence, of phosphatase[2]. Cell Viability Assay[2] Cell Line: Pancreatic cancer cell line: S2-013, MIA PaCa-2, S2-VP10, and Panc-1 cells
Minnelide (injection intraperitoneally; 0.1-0.6 mg/kg; once daily or twice daily) leads to a marked decrease in tumor weight and volume at the end of treatment and increases survival in orthotopic model of pancreatic cancer with MIA PaCa-2-derived human pancreatic tumors[2].Minnelide (injection intraperitoneally; 0.42 mg/kg; once daily; 28 days) prevents locoregional spread and leads to a decrease in average tumor weight in a xenograft model of pancreatic cancer with metastatic S2-013 cells[2].Minnelide (injection intraperitoneally; 0.42 mg/kg, 0.21 mg/kg; once daily) causes tumor regression and tumors from Minnelide-treated animals showed fibrosis and the presence of pyknotic nuclei in human pancreatic cancer xenografts in SCID mice[2]. Animal Model: Orthotopic model of pancreatic cancer with MIA PaCa 2-derived human pancreatic tumors in athymic nude mice[2]
[1]. Noel P，et al. Triptolide and Its Derivatives as Cancer Therapies. Trends Pharmacol Sci. 2019 May;40(5):327-341. [2]. Chugh R, et al. A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med. 2012 Oct 17;4(156):156ra139.
| Cas No. | 1254702-87-8 | SDF | |
| 别名 | 明奈利德 | ||
| Canonical SMILES | C[C@@]12[C@@]34[C@]([C@@H]5C[C@@]1([H])C6=C(C(OC6)=O)CC2)(O5)[C@@H]([C@](O7)(C(C)C)[C@@H]7[C@@H]3O4)OCOP(O[Na])(O[Na])=O | ||
| 分子式 | C21H25Na2O10P | 分子量 | 514.37 |
| 溶解度 | DMSO: 16.67 mg/mL (32.41 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9441 mL | 9.7206 mL | 19.4413 mL |
| 5 mM | 0.3888 mL | 1.9441 mL | 3.8883 mL |
| 10 mM | 0.1944 mL | 0.9721 mL | 1.9441 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Triptolide and Its Derivatives as Cancer Therapies
Trends Pharmacol Sci 2019 May;40(5):327-341.PMID:30975442DOI:10.1016/j.tips.2019.03.002.
Triptolide, a compound isolated from a Chinese medicinal herb, possesses potent antitumor, immunosuppressive, and anti-inflammatory properties, but is clinically limited due to its poor solubility, bioavailability, and toxicity. Recently, Minnelide, a water-soluble prodrug of triptolide, was shown to have potent antitumor activity in various preclinical cancer models. Minnelide is currently in Phase II clinical trials for treatment of advanced pancreatic cancer, which has fueled increased interest in this promising agent. Here, we review the recent advances in the biological activity of triptolide and its analogs, their mechanisms of actions, and their clinical developments. A special emphasis is given to proteins and pathways within the tumor and stromal compartments that are targeted by triptolide and its analogs as well as the ongoing clinical trials.
Minnelide, a novel drug for pancreatic and liver cancer
Pancreatology 2015 Jul;15(4 Suppl):S39-43.PMID:26122306DOI:10.1016/j.pan.2015.05.472.
Background: Pancreatic cancer is the 10th leading cause of all new cancer cases for men and the fourth leading cause of death across genders, having very poor prognosis and survival rates. The current standard of care Gemcitabine fails to add any survival benefit for this disease (www.cancer.gov). Though the incidence of pancreatic cancer is found to be higher in developed countries, the aggressive biology of the cancer, its high rate of recurrence and chemo-resistance make it a formidable disease in all parts of the globe. Hepatocellular carcinoma (HCC) or liver cancer, on the other hand affects almost 750,000 people world wide with 84% of the cases coming from underdeveloped or developing countries Results: Our studies show that Minnelide, a water soluble pro-drug of triptolide (active compound from a chinese herb) is very effective against a number of malignant diseases. Conclusion: The current study discusses the efficacy of this compound in pancreatic and liver cancer.
Minnelide, a prodrug, inhibits cervical cancer growth by blocking HPV-induced changes in p53 and pRb
Am J Cancer Res 2021 May 15;11(5):2202-2214.PMID:34094678doi
HPV-induced cervical cancer is one of the prevalent gynecological cancers world-wide. In the present study, we determined the efficacy of Minnelide, a prodrug which is converted to its active form (Triptolide) in vivo against cervical cancer cells. Our studies show that Triptolide inhibited HPV-16 and HPV-18 positive cells at nanomolar concentrations. Tumor cells treated with Triptolide failed to grow in 3-D cultures in a concentration-dependent manner. Triptolide markedly reduced E6 and E7 transcript levels. Further studies revealed that exposure to Triptolide increased the levels of p53 and pRb. As a consequence, Caspase-3/7 activation and apoptosis was induced in cervical cancer cells by Triptolide. Subsequently, we evaluated the efficacy of Minnelide in xenotransplantation models of cervical cancer. Minnelide at very low doses effectively inhibited the growth of established cervical cancers in all the three animal models tested. Furthermore, Minnelide treatment was more effective when combined with platinum-based chemotherapy. These studies show that Minnelide can be used to inhibit the growth of cervical cancer.
Minnelide synergizes with conventional chemotherapy by targeting both cancer and associated stroma components in pancreatic cancer
Cancer Lett 2022 Jul 1;537:215591.PMID:35398530DOI:10.1016/j.canlet.2022.215591.
Addition of nab-paclitaxel to gemcitabine offers a survival benefit of only 6 weeks over gemcitabine alone at a cost of increased toxicity in PDAC. The goal of the present study is to evaluate the efficacy of Minnelide, a water-soluble prodrug of triptolide, in combination with the standard of care regimen for chemotherapy with the added advantage of reducing the doses of these drugs to minimize toxicity. Pancreatic cancer cell lines were implanted subcutaneously or orthotopically in athymic nude or C57BL/6J mice. Subsequently, animals were randomized and received saline or Minnelide or full dose chemotherapy or low dose chemotherapy or Minnelide in combination with low dose chemotherapy. Our results show that a combination of low doses of Minnelide with Gemcitabine + nab-paclitaxel significantly inhibited tumor progression and increased the survival of tumor-bearing mice in comparison with conventional chemotherapy alone. Moreover, combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis and effectively targeted both cancer and the associated stroma. In vitro studies with a combination of low doses of triptolide and paclitaxel significantly decreased the cell viability, increased apoptosis and led to significantly increased M-phase cell cycle arrest in various pancreatic cancer cell lines as compared to either drug alone. Our results show that Minnelide synergizes with conventional chemotherapy leading to a significant reduction in the doses of these toxic drugs, all the while achieving better efficacy in the treatment of PDAC. This combination effectively targeted both the cancer and the associated stromal components of pancreatic cancer.
A phase II trial of the super-enhancer inhibitor Minnelide™ in advanced refractory adenosquamous carcinoma of the pancreas
Future Oncol 2022 Jun;18(20):2475-2481.PMID:PMC9344435DOI:10.2217/fon-2021-1609.
Adenosquamous carcinoma of the pancreas (ASCP) is a very rare and highly aggressive variant of pancreatic ductal adenocarcinoma, accounting for 0.5-4% of all pancreatic cancer cases in the USA. Current data indicate that epigenetic changes and MYC overexpression lead to squamous transdifferentiation of pancreatic tumor cells and development of ASCP. Minnelide™, an oral anti-super-enhancer drug that inhibits MYC expression in preclinical models of ASCP, has demonstrated safety in a phase I study. We describe the design for a phase II, open-label, single-arm trial of Minnelide in patients with advanced refractory ASCP.