Size | Price | Stock | Qty |
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1mg |
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5mg |
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Other Sizes |
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Targets |
U373MG cell (IC50 = 4.83 nM); HCT116 cell (IC50 = 0.6 nM); QG56 cell (IC50 = 2.4 nM); DU145 (IC50 = 0.81 nM)
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ln Vitro |
In U373MG cells, ecteinascidin 770 causes apoptosis. MTT testing shows that after 72 hours of treatment, ascidin 770 kills U373MG glioblastoma cells in culture with an IC50 concentration of 4.83 nM [1]. In relation to the human cell lines HCT116, QG56, and DU145, the IC50 values are, respectively, 0.6, 2.4, and 0.81 nM[2]. In a dose-dependent way, ET-770 can improve the anoikis response in human lung cancer H23 cells. By activating the p53 protein, ecteinascidin 770 sensitizes cells by upregulating the BCL2-associated X protein (BAX) and downregulating the anti-apoptotic myeloid cell leukemia sequence 1 (MCL1). Ecteinascidin 770 did not, however, have a substantial effect on the B-cell lymphoma-2 (BCL2) protein. In H460 lung cancer cells, the anoikis sensitization effect of ET-770 was detected [3].
Ecteinascidin 770 (ET-770) was shown to enhance anoikis response of human lung cancer H23 cells in a dose-dependent manner. The underlying mechanism was investigated and it was found that ET-770 sensitized the cells by activating the p53 protein, which in turn down-regulated anti-apoptotic myeloid cell leukemia sequence-1 (MCL1) and up-regulated BCL2-associated X protein (BAX) proteins. However, B-cell lymphoma-2 (BCL2) proteins were not significantly affected by ET-770. Further, the anoikis sensitization of ET-770 was observed in H460 lung cancer cells. Conclusion: The present results reveal for the first time that ET-770 can sensitize anoikis through the p53 pathway and further development of this compound for therapeutic use is warranted. [3] Background: Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin 770 (ET-770) (the compound 1a) and renieramycin M (RM; the compound 2a) from Thai marine invertebrates, together with a 2'-N-4"-pyridinecarbonyl derivative of ecteinascidin 770 (ET-770) (the compound 3). We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG. Methods: We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. Results: All of these compounds induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ecteinascidin 770 (ET-770) downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR) signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B. Conclusion: Molecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective drug targets [1]. |
Cell Assay |
Background: The strategies for achieving anti-metastasis have received increased research interest and clinical attention. The anoikis-sensitizing effect of ecteinascidin 770 (ET-770) was investigated in the present study in non-small cell lung cancer cells.
Materials and methods: ecteinascidin 770 (ET-770) isolated from Ecteinascidia thurstoni was tested for its anoikis-sensitizing effect on H23 and H460 human lung cancer cells by 2,3-b-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. The levels of proteins being involved in anoikis of cells were determined by western blot analysis [3]. Cell viability. [3] Cells were seeded into 96-well plates at 1×105 cell/ml for 24 h and then treated with different concentrations of ecteinascidin 770 (ET-770) for 24 h. Cells were then incubated with 20 μM of XTT reagent for a further 4 h at 37°C. The intensity of the formazan product was measured at 450 nm using a microplate reader. All analyses were established in at least three independent replicate cultures. The cell viability was calculated from the optical density (OD) ratio of treated to non-treated control cells and is presented as a percentage to that of the non-treated controls. |
References |
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Additional Infomation |
Ecteinascidin 770 has been reported in Ecteinascidia thurstoni and Ecteinascidia turbinata with data available.
A three-step transformation of ecteinascidin 770 (1b) into 2'-N-indole-3-carbonyl derivative 3 via 18,6'-O-bisallyl-protected derivative 4a, which was shown to have higher cytotoxicity than 1b, is presented. In addition, a number of 2'-N amide derivatives of 1b have been prepared from 4a and their in vitro cytotoxicity were determined by measuring IC₅₀ values against human cell lines HCT116, QG56, and DU145. Benzoyl amide derivatives 7a-c showed similar in vitro cytotoxicity to 1b, whereas the nitrogen-containing heterocyclic derivatives 7d-h and cinnamoyl derivatives 9a-b showed higher cytotoxicity than 1b. In contrast, the 18,6'-O-bisallyl protected derivatives 4a-c, 6a-h, and 8a-b showed dramatic decreases in cytotoxicity relative to 1b.[2] |
Molecular Formula |
C40H42N4O10S
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Molecular Weight |
770.84700
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Exact Mass |
770.262
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CAS # |
114899-80-8
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PubChem CID |
10952807
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Appearance |
White to off-white solid powder
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Source |
Ecteinascidia thurstoni and Ecteinascidia turbinata
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LogP |
4.191
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Hydrogen Bond Donor Count |
3
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Hydrogen Bond Acceptor Count |
15
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Rotatable Bond Count |
4
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Heavy Atom Count |
55
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Complexity |
1550
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Defined Atom Stereocenter Count |
7
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SMILES |
CC1=CC2=C([C@@H]3[C@@H]4[C@H]5C6=C(C(=C7C(=C6[C@@H](N4[C@H]([C@H](C2)N3C)C#N)COC(=O)[C@@]8(CS5)C9=CC(=C(C=C9CCN8)O)OC)OCO7)C)OC(=O)C)C(=C1OC)O
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InChi Key |
BGFXHQYUWCGGLL-QWIBJBKUSA-N
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InChi Code |
InChI=1S/C40H42N4O10S/c1-17-9-21-10-23-24(13-41)44-25-14-51-39(48)40(22-12-27(49-5)26(46)11-20(22)7-8-42-40)15-55-38(32(44)31(43(23)4)28(21)33(47)34(17)50-6)30-29(25)37-36(52-16-53-37)18(2)35(30)54-19(3)45/h9,11-12,23-25,31-32,38,42,46-47H,7-8,10,14-16H2,1-6H3/t23-,24-,25-,31+,32+,38+,40+/m0/s1
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Chemical Name |
[(1R,2R,3R,11S,12R,14R,26R)-12-cyano-5,6'-dihydroxy-6,7'-dimethoxy-7,21,30-trimethyl-27-oxospiro[17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.13,11.02,13.04,9.015,23.016,20]triaconta-4(9),5,7,15,20,22-hexaene-26,1'-3,4-dihydro-2H-isoquinoline]-22-yl] acetate
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Synonyms |
Ecteinascidin 770; 114899-80-8; [(1R,2R,3R,11S,12R,14R,26R)-12-cyano-5,6'-dihydroxy-6,7'-dimethoxy-7,21,30-trimethyl-27-oxospiro[17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.13,11.02,13.04,9.015,23.016,20]triaconta-4(9),5,7,15,20,22-hexaene-26,1'-3,4-dihydro-2H-isoquinoline]-22-yl] acetate; Ecteinascidin770; ((1R,2R,12R,14R,26R)-12-cyano-5,6'-dihydroxy-6,7'-dimethoxy-7,21,30-trimethyl-27-oxospiro(17,19,28-trioxa-24-thia-13,30-diazaheptacyclo(12.9.6.13,11.02,13.04,9.015,23.016,20)triaconta-4(9),5,7,15,20,22-hexaene-26,1'-3,4-dihydro-2H-isoquinoline)-22-yl) acetate; ((1R,2R,3R,11S,12R,14R,26R)-12-cyano-5,6'-dihydroxy-6,7'-dimethoxy-7,21,30-trimethyl-27-oxospiro(17,19,28-trioxa-24-thia-13,30-diazaheptacyclo(12.9.6.13,11.02,13.04,9.015,23.016,20)triaconta-4(9),5,7,15,20,22-hexaene-26,1'-3,4-dihydro-2H-isoquinoline)-22-yl) acetate; (1R,2R,3R,11S,12S,14R,26R)-5,6'-Dihydroxy-6,7'-dimethoxy-7,12,21,30-tetramethyl-27-oxo-3',4'-dihydro-2'H-17,19,28-trioxa-24-thia-13,30-diazaspiro(heptacyclo(12.9.6.1,.0,.0,.0,.0,)triacontane-26,1'-isoquinoline)-4(9),5,7,15(23),16(20),21-hexaen-22-yl acetic acid; (1R,2R,3R,11S,12S,14R,26R)-5,6'-Dihydroxy-6,7'-dimethoxy-7,12,21,30-tetramethyl-27-oxo-3',4'-dihydro-2'H-17,19,28-trioxa-24-thia-13,30-diazaspiro[heptacyclo[12.9.6.1,.0,.0,.0,.0,]triacontane-26,1'-isoquinoline]-4(9),5,7,15(23),16(20),21-hexaen-22-yl acetic acid;
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~50 mg/mL (~64.86 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.2973 mL | 6.4863 mL | 12.9727 mL | |
5 mM | 0.2595 mL | 1.2973 mL | 2.5945 mL | |
10 mM | 0.1297 mL | 0.6486 mL | 1.2973 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.