Mifamurtide
(Synonyms: 米伐木肽; MTP-PE; L-MTP-PE; CGP 19835) 目录号 : GC36609
Mifamurtide(CGP19835; MTP-PE)可作用于骨肉瘤。
Cas No.:83461-56-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mifamurtide(CGP19835; MTP-PE) is a drug against osteosarcoma.Target: OthersMifamurtide is an immunomodulator with antitumor effects that appear to be mediated via activation of monocytes and macrophages. Mifamurtide is generally well tolerated; adverse events attributed to administration of the drug include chills, fever, headache, nausea, and myalgias. Based on the available data, mifamurtide can be considered for inclusion in treatment protocols for localized osteosarcoma [1]. Mifamurtide has orphan drug status for the treatment of osteosarcoma in the US and EU [2].
[1]. Frampton, J.E., Mifamurtide: a review of its use in the treatment of osteosarcoma. Paediatr Drugs, 2010. 12(3): p. 141-53. [2]. Mifamurtide: CGP 19835, CGP 19835A, L-MTP-PE, liposomal MTP-PE, MLV 19835A, MTP-PE, muramyltripeptide phosphatidylethanolamine. Drugs R D, 2008. 9(2): p. 131-5.
| Cas No. | 83461-56-7 | SDF | |
| 别名 | 米伐木肽; MTP-PE; L-MTP-PE; CGP 19835 | ||
| Canonical SMILES | CCCCCCCCCCCCCCCC(OC[C@@H](OC(CCCCCCCCCCCCCCC)=O)COP(OCCNC([C@@H](NC(CC[C@@H](NC([C@@H](NC([C@H](O[C@]([C@H](O)[C@H](O)CO)([H])[C@H](C=O)NC(C)=O)C)=O)C)=O)C(N)=O)=O)C)=O)(O)=O)=O | ||
| 分子式 | C59H109N6O19P | 分子量 | 1237.5 |
| 溶解度 | DMSO: ≥ 100 mg/mL (80.81 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 | 0.8081 mL | 4.0404 mL | 8.0808 mL |
| 5 mM | 0.1616 mL | 0.8081 mL | 1.6162 mL |
| 10 mM | 0.0808 mL | 0.404 mL | 0.8081 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。
Mifamurtide: a review of its use in the treatment of osteosarcoma
Paediatr Drugs 2010 Jun;12(3):141-53.PMID:20481644DOI:10.2165/11204910-000000000-00000.
Mifamurtide (liposomal muramyl tripeptide phosphatidyl ethanolamine; Mepact) is an immunomodulator with antitumor effects that appear to be mediated via activation of monocytes and macrophages. In the EU, Mifamurtide is indicated in children, adolescents, and young adults for the treatment of high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection; it is administered by intravenous infusion in conjunction with postoperative multiagent chemotherapy. In the US, Mifamurtide is currently an investigational agent that holds orphan drug status for the treatment of osteosarcoma. In a large, randomized, open-label, multicenter, phase III trial, the addition of adjuvant (postoperative) Mifamurtide to three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with a statistically significant improvement in overall survival in patients with newly diagnosed, high-grade, non-metastatic, resectable osteosarcoma. The pattern of outcome was generally similar in a small cohort of patients with metastatic disease who were enrolled in this trial. Mifamurtide is generally well tolerated; adverse events attributed to administration of the drug include chills, fever, headache, nausea, and myalgias. Based on the available data, Mifamurtide can be considered for inclusion in treatment protocols for localized osteosarcoma.
Translational biology of osteosarcoma
Nat Rev Cancer 2014 Nov;14(11):722-35.PMID:25319867DOI:10.1038/nrc3838.
For the past 30 years, improvements in the survival of patients with osteosarcoma have been mostly incremental. Despite evidence of genomic instability and a high frequency of chromothripsis and kataegis, osteosarcomas carry few recurrent targetable mutations, and trials of targeted agents have been generally disappointing. Bone has a highly specialized immune environment and many immune signalling pathways are important in bone homeostasis. The success of the innate immune stimulant Mifamurtide in the adjuvant treatment of non-metastatic osteosarcoma suggests that newer immune-based treatments, such as immune checkpoint inhibitors, may substantially improve disease outcome.
Mifamurtide: CGP 19835, CGP 19835A, L-MTP-PE, liposomal MTP-PE, MLV 19835A, MTP-PE, muramyltripeptide phosphatidylethanolamine
Drugs R D 2008;9(2):131-5.PMID:18298131DOI:10.2165/00126839-200809020-00007.
Mifamurtide is a conjugate of muramyl tripeptide linked to dipalmitoyl phosphatidyl ethanolamine; the phospholipid facilitates incorporation of the peptide into liposomes. The agent stimulates macrophages to seek out and destroy cancer cells. The compound was originated by Novartis (formerly CIBA-Geigy), and is being developed by IDM Pharma for osteosarcoma. Mifamurtide is being reviewed by regulatory authorities in the US and EU for this indication.CIBA-Geigy originally developed Mifamurtide in the early 1980s and the agent was subsequently outlicensed to Jenner Biotherapies in the 1990s. IDM Pharma acquired the rights to the drug from Jenner in April 2003.IDM and Genesis Pharma have entered into an exclusive licensing and marketing agreement for Mifamurtide in South East Europe. Under the agreement terms, IDM will receive an upfront fee from Genesis, as well as milestone payments on reaching certain sales levels in the territory. Medison Pharma signed an agreement with IDM Pharma for the sales and marketing of Mifamurtide in Israel. IDM will receive an upfront license fee from Medison and will be entitled to receive a milestone payment upon regulatory approval of the agent in Israel, as well as royalties on net sales.IDM outlicensed exclusive marketing rights for Mifamurtide in the UK and Ireland to Cambridge Laboratories in June 2005. In exchange, IDM is entitled to an upfront license fee and milestone payments prior to launch, as well as royalties calculated on product sales.Previously, Chiron Vaccines (a joint venture between Novartis and Chiron formed in 1995) investigated Mifamurtide as an adjuvant in HIV gp120 vaccine; however, development has been discontinued.IDM Pharma will purchase approximately 7.1 million shares of its common stock to raise approximately $US23.5 million in net proceeds. The company intends to use the funds for working capital and corporate purposes, including the company's activities related to gaining marketing approval of Mifamurtide in the US and Europe. Following the announcement by ODAC in May 2007, IDM Pharma decided to amend the NDA for Mifamurtide with additional vital status data from the completed phase III trial. This data was not available at the time the original filing was made, and the company believes that capturing this supplemental data will overcome the need for additional trials, further confirm the overall survival benefit of Mifamurtide in osteosarcoma, and provide evidence for approvability. IDM Pharma intends to analyse the additional follow-up data and submit an amendment to the agency by the first quarter of 2008; the company is also working on addressing other concerns raised by the US FDA in the non-approvable letter. The US regulatory submission included safety and efficacy data from NCI-funded phase III trials in 678 patients with osteosarcoma conducted by the Pediatric Oncology Group and the Children's Cancer Group in over 147 US centres. The NDA also included safety and biological effects data of Mifamurtide from 17 phase I and II studies in 248 patients conducted by Ciba-Geigy. In the EU, IDM Pharma filed a MAA with the EMEA in November 2006 for approval of Mifamurtide (Mepacttrade mark) in combination with postoperative chemotherapy for the treatment of patients with newly diagnosed osteosarcoma following complete surgical resection. The company expects that the EMEA will make a decision regarding marketing approval for Mifamurtide by the end of 2007. Mifamurtide has orphan drug status for the treatment of osteosarcoma in the US and EU.
Mifamurtide in osteosarcoma--a practical review
Drugs Today (Barc) 2010 May;46(5):327-37.PMID:20517534DOI:10.1358/dot.2010.46.5.1500076.
Mifamurtide, also known as liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE), has been approved for the treatment of osteosarcoma in Europe. Mifamurtide's rational drug design employs MTP-PE for macrophage activation in a multilamellar liposome drug carrier, containing the synthetic phospholipids 1-palmitoyl-2-oleoyl phosphatidyl choline (POPC) and 1,2-dioleoyl phosphatidyl serine (OOPS). Although the drug is not cytotoxic towards normal or tumor cells in vitro, immune activation against osteosarcoma lung metastases in vivo accounts for Mifamurtide's antiosteosarcoma effects. Phosphatidyl serine-containing lipids signal macrophage cells that have "flipped phosphatidyl serine" to the outer membrane after apoptosis (e.g., after damage of tumor cells from chemotherapy); thus, both Mifamurtide's active and inactive ingredients target immune cells in the lungs. Mifamurtide administration has resulted in 8% and 13% improvement in 6- and 5-year overall survivals, when added to chemotherapy in nonmetastatic and metastatic patients with osteosarcoma, respectively. The short-term toxicities of Mifamurtide (fever, headache, flu-like symptoms and rigors) are reduced or eliminated using ibuprofen (200 mg) as premedication for the first infusion; an algorithm for pre- and postmedication is presented. To date, no long-term side effects of Mifamurtide have been reported. Compassionate access programs based in two major cancer centers (MD Anderson and Memorial Sloan-Kettering), have recently provided this potentially life-saving drug in North America. The experience with Mifamurtide provides an outstanding example of successful cooperation among regulatory bodies and agencies, the pharmaceutical industry and pediatric oncologists to improve cancer care and outcomes for children and young people with a rare sarcoma.
Effectiveness of Mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review
JBI Database System Rev Implement Rep 2017 Aug;15(8):2113-2152.PMID:28800058DOI:10.11124/JBISRIR-2016-003105.
Background: Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy. Therefore, there is a critical need for more effective and innovative therapeutic approaches such as immune stimulatory agents. The most extensively studied immune stimulatory agent in the treatment of osteosarcoma is Mifamurtide. The aim of this systematic review was to identify and synthesize the evidence on the effectiveness of Mifamurtide in addition to standard chemotherapy on survival outcomes. Objectives: To present the best available evidence on the treatment of high-grade non-metastatic and metastatic osteosarcoma with Mifamurtide in addition to standard chemotherapy. Inclusion criteria types of participants: All populations of patients regardless of age, gender or ethnicity with high-grade, resectable, non-metastatic and metastatic osteosarcoma based on histological diagnosis. Types of interventions and comparators: This review focused on intravenous infusion of either of the pharmaceutical formulations of Mifamurtide (MTP-PE or L-MTP-PE) in addition to standard chemotherapy, and the comparator was chemotherapy alone. Types of studies: This review considered any experimental study design including randomized controlled trials, non-randomized trials and quasi-experimental studies. Outcomes: The primary outcomes of interest were event-free survival, overall survival and recurrence of osteosarcoma. Secondary outcomes that were considered included health-related quality of life and any mifamurtide-related adverse events. Search strategy: A search for published and unpublished literature in English was undertaken (seven published literature databases, four unpublished literature databases, and three government agency and organizational websites were searched). Studies published between 1990 to June 2016 were considered. A three-step strategy was developed using MeSH terminology and keywords to ensure that all relevant studies were included related to this review. Methodological quality: The methodological quality of included studies was assessed by two reviewers, who appraised each study independently, using a standardized Joanna Briggs Institute (JBI) critical appraisal tool. Data extraction: Data was extracted from the studies that were identified as meeting the criteria for methodological quality using the standard JBI data extraction tool. Data synthesis: Due to the heterogeneity of populations and interventions in available studies, meta-analysis was not possible and results are presented in narrative form. Results: Three papers outlining two studies involving 802 patients evaluated the effectiveness of Mifamurtide in addition of chemotherapy. Results indicated no significant difference in event-free survival between the addition of Mifamurtide to standard chemotherapy regimen and chemotherapy alone, both in non-metastatic and metastatic osteosarcoma patients. There was a significant difference in progression-free survival favoring the addition of Mifamurtide in pulmonary metastatic and/or relapsed osteosarcoma. There was no significant difference in overall survival between the addition of Mifamurtide and chemotherapy alone in metastatic osteosarcoma; however there was a significant difference favoring the addition of Mifamurtide in non-metastatic osteosarcoma patients. The addition of Mifamurtide resulted in a significant difference in survival after relapse in pulmonary metastatic and/or relapsed osteosarcoma patients. Both studies reported on mifamurtide-related adverse events - the first was reported as toxicity which included haematological, hepatic, renal, gastrointestinal disorders, cardiac, rhythm and nervous system disorders, ear disorders and others (infection, fever; and performance status) in metastatic osteosarcoma patients. Results were similar across all combined treatment regimens. Although no statistical analysis was undertaken, the figures suggest there were no significant differences between the treatment regimens. In the other study, mifamurtide-related adverse events were reported as clinical toxic effects of Mifamurtide in relapsed osteosarcoma, which included chills, fever and headache for the initial dose of Mifamurtide, while for the subsequent doses of Mifamurtide all patients reported toxicity as delayed fatigue. Conclusions: The available evidence on the effectiveness of Mifamurtide in addition to a standard chemotherapy regimen for the treatment of high-grade osteosarcoma is limited and therefore no definitive conclusions can be made.