Fostriecin sodium salt |
| カタログ番号GC14395 |
A potent inhibitor of protein phosphatases 2A and 4
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 87860-39-7
Sample solution is provided at 25 µL, 10mM.
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IC50: Inhibit protein phosphatase types 2A (PP2A) and 4 (PP4) intensively with an IC50 of 1.5 nM and 3 nM respectively. Inhibit topoisomerase II (Topo II) and protein phosphatase type 1 (PP1) slightly with an IC50 of 40 μM and 131 μM respectively.
Fostriecin, an anti-tumor antibiotic originates from Streptomyces pulveraceus, is considered to exert its activity by interfering the reversible phosphorylation of several important proteins in cell cycle. Fostriecin sodium salt also exhibits anti-tumor activity via suppressing enzymes including PP2A, PP4, PP1 and Topo II. [1]
In vitro: A human tumor cloning assay was adopted to investigate the antineoplastic activity of fostriecin. Variety of histologic tumor cells exposure to 10 mg/ml fostriecin resulted in 27% in vitro anticancer response. In another study using HeLa cells, by suppressing the Topo II catalytic activity, 0.22 mM fostriecin could lead to more than 90% inhibition of cancer cell DNA synthesis. [2,3]
In vivo: Fostriecin showed intensively cytotoxicity against a number of cancer cell lines and had a strong antitumor effect in animals. 10 mg/ml fostriecin could substantially suppress P388 and L1210 leukemias in mice. [2,3]
Clinical trial: Fostriecin reached clinical phase I study sponsored by the National Cancer Institute to investigate its antitumor activity in human. With dosages escalated from 2 to 20 mg/m2/day, fostriecin was administered as a 60-min intravenous (IV) infusion to 20 patients in cancer for 5 days. Although the trials were suspended due to the concerns about the storage stability of this naturally originated compound, this discovery ignited a broad interest in derivatives of fostriecin. [1,4]
References:
[1] Zhang X, Wu J, Fang L, Willis WD. The effects of protein phosphatase inhibitors on the duration of central sensitization of rat dorsal horn neurons following injection of capsaicin. Mol Pain. 2006 Jul; 2(23). DOI:10.1186/1744-8069-2-23.
[2] Scheithauer W, Von Hoff DD, Clark G, Shillis JL, Elslager EF. In vitro activity of the novel antitumor antibiotic fostriecin (CI-920) in a human tumor cloning assay. Eur J Cancer Res & Clin Oncol. 1986 Aug; 22(8): 921-6.
[3] Gedik CM, Collins AR. Comparison of effects of fostriecin, novobiocin, and camptothecin, inhibitors of DNA topoisomerases, on DNA replication and repair in human cells. Nnucleic Acids Res. 1990 Aug; 18(4):1008-13.
[4] Le LH, Erlichman C, Pillon L, Thiessen JJ, Day A, Wainman N, Eisenhauer EA, Moore MJ. Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.
Invest New Drugs. 2004 Apr; 22(2):159-67.
| Cell experiment[1]: | |
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Cell lines |
HeLa cells |
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Preparation method |
The solubility of this compound in sterile water is 100 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
30 min, 0.22 mM |
|
Applications |
Fostriecin is an inhibitor of topoisomerase II. It blocks an early step in the reaction and does not accumulate broken DNA intermediates. Fostriecin causes a strong but delayed inhibition of DNA synthesis in human Hela cells. |
| Animal experiment [2]: | |
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Animal models |
B6D2F1 mice with subcutaneous Colon 38 tumours. |
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Dosage form |
Intraperitoneal injection, 65 mg/kg |
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Application |
When administered as a single dose, fostriecin caused extensive necrosis of tumours after 24 h and induced significant delays in the growth of advanced subcutaneous tumours by at least 10 days. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Gedik C M, Collins A R. Comparison of effects of fostriecin, novobiocin, and camptothecin, inhibitors of DNA topoisomerases, on DNA replication and repair in human cells[J]. Nucleic acids research, 1990, 18(4): 1007-1013. [2]. Baguley B C, Calveley S B, Crowe K K, et al. Comparison of the effects of flavone acetic acid, fostriecin, homoharringtonine and tumour necrosis factor α on colon 38 tumours in mice[J]. European Journal of Cancer and Clinical Oncology, 1989, 25(2): 263-269. |
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| Cas No. | 87860-39-7 | SDF | |
| Chemical Name | sodium;[(3R,4R,6R,7E,9E,11E)-3,6,13-trihydroxy-3-methyl-1-[(2R)-6-oxo-2,3-dihydropyran-2-yl]trideca-1,7,9,11-tetraen-4-yl] hydrogen phosphate | ||
| Canonical SMILES | CC(C=CC1CC=CC(=O)O1)(C(CC(C=CC=CC=CCO)O)OP(=O)(O)[O-])O.[Na+] | ||
| Formula | C19H26O9PNa | M.Wt | 452.37 |
| 溶解度 | Soluble in Water | Storage | Desiccate at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2106 mL | 11.0529 mL | 22.1058 mL |
| 5 mM | 0.4421 mL | 2.2106 mL | 4.4212 mL |
| 10 mM | 0.2211 mL | 1.1053 mL | 2.2106 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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