Migrastatin
(Synonyms: (+)-Migrastatin) 目录号 : GC48479
A fungal metabolite with antimuscarinic and anticancer activities
Cas No.:314245-65-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Migrastatin is a bacterial metabolite that has been found in Streptomyces with antimuscarinic and anticancer activities.1,2 It binds to M1-5 muscarinic acetylcholine receptors (Kis = >200, 200, 31, 43, and >200 µM, respectively) and inhibits calcium mobilization induced by carbamoylcholine in SK-N-SH cells (IC50 = 28 µM), as well as in primary rat bladder smooth muscle cells.1 Migrastatin inhibits the migration of EC17 esophageal cancer cells in a wound healing assay (IC50 = 10 µg/ml) and 4T1 mouse mammary carcinoma cells in a chamber cell migration assay (IC50 = 29 µM).2 It enhances cytotoxicity induced by vinblastine in vincristine-resistant P388/VCR cells.3
1.Nakae, K., Nishimura, Y., Ohba, S., et al.Migrastatin acts as a muscarinic acetylcholine receptor antagonistJ. Antibiot. (Tokyo)59(11)685-692(2006) 2.Reymond, S., and Cossy, J.Migrastatin and analogues: New anti-metastatic agentsC. R. Chim.11(11-12)1447-1462(2008) 3.Takemoto, Y., Tashiro, E., and Imoto, M.Suppression of multidrug resistance by migrastatinJ. Antibiot. (Tokyo)59(7)435-438(2006)
| Cas No. | 314245-65-3 | SDF | |
| 别名 | (+)-Migrastatin | ||
| Canonical SMILES | O=C(NC(C1)=O)CC1CCCC([C@H]([C@]2([H])/C(C)=C\[C@H]([C@@H]([C@H](/C=C/CC/C=C/C(O2)=O)OC)O)C)C)=O | ||
| 分子式 | C27H39NO7 | 分子量 | 489.6 |
| 溶解度 | DMF: soluble,DMSO: soluble,Methanol: soluble | 储存条件 | -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 | 2.0425 mL | 10.2124 mL | 20.4248 mL |
| 5 mM | 0.4085 mL | 2.0425 mL | 4.085 mL |
| 10 mM | 0.2042 mL | 1.0212 mL | 2.0425 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。
The Therapeutic Potential of Migrastatin-Core Analogs for the Treatment of Metastatic Cancer
Molecules 2017 Feb 9;22(2):198.PMID:28208778DOI:10.3390/molecules22020198.
Tumor metastasis is a complex process in which cells detach from the primary tumor and colonize a distant organ. Metastasis is also the main process responsible for cancer-related death. Despite the enormous efforts made to unravel the metastatic process, there is no effective therapy, and patients with metastatic tumors have poor prognosis. In this regard, there is an urgent need for new therapeutic tools for the treatment of this disease. Small molecules with the capacity to reduce cell migration could be used to treat metastasis. Migrastatin-core analogs are naturally inspired macrocycles that inhibit pathological cell migration and are able to reduce metastasis in animal models. Migrastatin analogs can be synthesized from a common advanced intermediate. Herein we present a review of the synthetic approaches that can be used to prepare this key intermediate, together with a review of the biological activity of migrastatin-core analogs and current hypotheses concerning their mechanism of action.
Migrastatin analogues target fascin to block tumour metastasis
Nature 2010 Apr 15;464(7291):1062-6.PMID:20393565DOI:10.1038/nature08978.
Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized Migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these Migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that Migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.
Migrastatin acts as a muscarinic acetylcholine receptor antagonist
J Antibiot (Tokyo) 2006 Nov;59(11):685-92.PMID:17256466DOI:10.1038/ja.2006.91.
Migrastatin and its analogs have various biological activities such as inhibition of cell migration and anchorage-independent growth of cancer cells. Although its biosynthesis and chemical synthesis have been under investigation, little is known about the biological target of Migrastatin. Here, we found that Migrastatin inhibited intracellular calcium mobilization induced by carbachol in neuroblastoma SK-N-SH cells without affecting Ca2+ mobilization and cAMP accumulation induced by ligands of other receptors. The binding of [3H] N-methylscopolamine, an antagonist for muscarinic receptor was also inhibited by migrastain. Functionally, Migrastatin inhibited Ca2+ mobilization induced by carbachol in primary cultures of smooth muscle cells of rat bladder. This study reveals that Migrastatin acts as a muscarinic acetylcholine receptor antagonist.
Migrastatin analogues inhibit canine mammary cancer cell migration and invasion
PLoS One 2013 Oct 8;8(10):e76789.PMID:24116159DOI:10.1371/journal.pone.0076789.
Background: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, Migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six Migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. Results: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF Migrastatin: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. Conclusion: Two synthetic Migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in vivo studies are required to verify this hypothesis.
iso-Migrastatin, Migrastatin, and dorrigocin production in Streptomyces platensis NRRL 18993 is governed by a single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase
J Biol Chem 2009 Oct 23;284(43):29746-56.PMID:19726666DOI:10.1074/jbc.M109.046805.
iso-Migrastatin and related glutarimide-containing polyketides are potent inhibitors of tumor cell migration and their implied potential as antimetastatic agents for human cancers has garnered significant attention. Genome scanning of Streptomyces platensis NRRL 18993 unveiled two candidate gene clusters (088D and mgs); each encodes acyltransferase-less type I polyketide synthases commensurate with iso-migrastatin biosynthesis. Both clusters were inactivated by lambda-RED-mediated PCR-targeting mutagenesis in S. platensis; iso-migrastatin production was completely abolished in the DeltamgsF mutant SB11012 strain, whereas inactivation of 088D-orf7 yielded the SB11006 strain that exhibited no discernible change in iso-migrastatin biosynthesis. These data indicate that iso-migrastatin production is governed by the mgs cluster. Systematic gene inactivation allowed determination of the precise boundaries of the mgs cluster and the essentiality of the genes within the mgs cluster in iso-migrastatin production. The mgs cluster consists of 11 open reading frames that encode three acyltransferase-less type I polyketide synthases (MgsEFG), one discrete acyltransferase (MgsH), a type II thioesterase (MgsB), three post-PKS tailoring enzymes (MgsIJK), two glutarimide biosynthesis enzymes (MgsCD), and one regulatory protein (MgsA). A model for iso-migrastatin biosynthesis is proposed based on functional assignments derived from bioinformatics and is further supported by the results of in vivo gene inactivation experiments.