Ingenol Mebutate (Ingenol 3-angelate)
(Synonyms: 巨大戟醇甲基丁烯酸酯; Ingenol 3-angelate; PEP005) 目录号 : GC31656
A natural cytotoxic diterpene ester
Cas No.:75567-37-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | KG1a cells are transiently transfected with EGFP-tagged mouse PKC-δ subcloned into pEGFP-N1 plasmid using an Amaxa nucleofection apparatus. Cells are treated with Ingenol Mebutate (0.2 μM-20 μM) 24 hours after transfection. Cell viability in EGFP-positive cells is assessed and loss of viability confirmed in the total cell culture by MTT assay after 3 days. Briefly, 24 hours after transfection, 2 × 104 cells are plated in 5 wells in 96-well plates and exposed to 0, 0.2, 2, and 20 μM Ingenol Mebutate. At 72 hours, 20 μL MTT substrate at 5 mg/mL is added and plates are incubated at 37°C. After 3 hours, 150 μL media is removed and replaced with 200 μL dimethyl sulfoxide (DMSO). Absorbance at an optical density (OD) of 550 nm is read on a plate reader and corrected for absorbance obtained from blank media controls[2]. |
References: [1]. Kedei N, et al. Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res. 2004 May 1;64(9):3243-55. | |
Ingenol-
1.Ogbourne, S.M., Suhrbier, A., Jones, B., et al.Antitumor activity of 3-ingenyl angelate: Plasma membrane and mitochondrial disruption and necrotic cell deathCancer Res.64(8)2833-2839(2004) 2.Gillespie, S.K., Zhang, X.D., and Hersey, P.Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in melanoma cellsMol. Cancer Ther.3(12)1651-1658(2004) 3.Li, L., Shukla, S., Lee, A., et al.The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculatureCancer Res.70(11)4509-4519(2010) 4.Hasler, C.M., Acs, G., and Blumberg, P.M.Specific binding to protein kinase C by ingenol and its induction of biological responsesCancer Res.52(1)202-208(1992) 5.Lebwohl, M., Swanson, N., Anderson, L.L., et al.Ingenol mebutate gel for actinic keratosisN. Engl. J. Med.366(11)1010-1019(2012) 6.Micali, G., Lacarrubba, F., Nasca, M.R., et al.Topical pharmacotherapy for skin cancer. Part I. PharmacologyJ. Am. Acad. Dermatol.70(6)965.e961-956.e912(2014)
| Cas No. | 75567-37-2 | SDF | |
| 别名 | 巨大戟醇甲基丁烯酸酯; Ingenol 3-angelate; PEP005 | ||
| Canonical SMILES | C/C=C(C)\C(O[C@H]1C(C)=C[C@]23[C@]1(O)[C@H](O)C(CO)=C[C@@](C3=O)([H])[C@@]4([H])[C@@](C4(C)C)([H])C[C@H]2C)=O | ||
| 分子式 | C25H34O6 | 分子量 | 430.53 |
| 溶解度 | DMSO : ≥ 100 mg/mL (232.27 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 | 2.3227 mL | 11.6136 mL | 23.2272 mL |
| 5 mM | 0.4645 mL | 2.3227 mL | 4.6454 mL |
| 10 mM | 0.2323 mL | 1.1614 mL | 2.3227 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。
Ingenol Mebutate
Topical ingenol mebutate has not been studied during breastfeeding. However, after topical administration, serum concentrations were undetectable, so breastfeeding is not expected to result in exposure of the breastfed infant. If ingenol mebutate is required by the mother, it is not a reason to discontinue breastfeeding. Do not apply ingenol mebutate to the breast or nipple and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated.
Medically Useful Plant Terpenoids: Biosynthesis, Occurrence, and Mechanism of Action
Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However, these highly functionalized natural products are produced through complex biosynthetic pathways for which we have a complete understanding in only a few cases. Here we review some of the most effective and promising plant terpenoids that are currently used in medicine and medical research and provide updates on their biosynthesis, natural occurrence, and mechanism of action in the body. This includes pharmacologically useful plastidic terpenoids such as p-menthane monoterpenoids, cannabinoids, paclitaxel (taxol?), and ingenol mebutate which are derived from the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, as well as cytosolic terpenoids such as thapsigargin and artemisinin produced through the mevalonate (MVA) pathway. We further provide a review of the MEP and MVA precursor pathways which supply the carbon skeletons for the downstream transformations yielding these medically significant natural products.
Randomized Trial of Four Treatment Approaches for Actinic Keratosis
Background: Actinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred.
Methods: We investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm2, were enrolled at four Dutch hospitals. Patients were randomly assigned to treatment with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with a reduction of 75% or more in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment. Both a modified intention-to-treat analysis and a per-protocol analysis were performed.
Results: A total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (P≿.001 for all comparisons). No unexpected toxic effects were documented.
Conclusions: At 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments. (Funded by the Netherlands Organization for Health Research and Development; ClinicalTrials.gov number, NCT02281682.).
Ingenol Mebutate: Expanded Utility
Ingenol mebutate (IM) is a novel drug that was developed for the treatment of actinic keratosis (AK). The drug works by a dual mechanism of action -- a rapid induction of cell death by necrosis along with a delayed neutrophil-mediated cellular cytotoxicity response.? Currently, IM is available as a 0.015% or 0.05% topical gel and has only been FDA-approved for the treatment of actinic keratosis. However, IM has also been extensively used off-label, and found to be efficacious in the treatment of multiple other skin disorders. In this review, we discuss the current literature that provides evidence for the successful use of ingenol mebutate as treatment for dermatologic disorders beyond actinic keratosis. J Drugs Dermatol. 2020;19(2)156-161. doi:10.36849/JDD.2020.4731
Ingenol Mebutate and the Treatment of Actinic Keratosis
Actinic keratoses (AKs) are common skin lesions association with increased exposure to ultraviolet radiation; these lesions have the potential to transform into squamous cell carcinomas (SCCs).1.