yingweiwo

Ecteinascidin 770

Alias: 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;
Cat No.:V33766 Purity: ≥98%
Ecteinascidin 770 (ET-770) is a 1,2,3,4-tetrahydroisoquinoline alkaloid with anti-cancer effect, and its IC50 for inhibiting U373MG cells is 4.83 nM.
Ecteinascidin 770
Ecteinascidin 770 Chemical Structure CAS No.: 114899-80-8
Product category: New2
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
Other Sizes
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text

 

  • Business Relationship with 5000+ Clients Globally
  • Major Universities, Research Institutions, Biotech & Pharma
  • Citations by Top Journals: Nature, Cell, Science, etc.
Top Publications Citing lnvivochem Products
Product Description
Ecteinascidin 770 (ET-770) is a 1,2,3,4-tetrahydroisoquinoline alkaloid with anti-cancer effect, and its IC50 for inhibiting U373MG cells is 4.83 nM.
Biological Activity I Assay Protocols (From Reference)
Targets
U373MG cell (IC50 = 4.83 nM); HCT116 cell (IC50 = 0.6 nM); QG56 cell (IC50 = 2.4 nM); DU145 (IC50 = 0.81 nM)
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

[1]. Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids. Cancer Cell Int. 2012 Apr 11;12(1):14.

[2]. Chemistry of ecteinascidins. Part 3: preparation of 2'-N-acyl derivatives of ecteinascidin 770 and evaluation of cytotoxicity. Bioorg Med Chem. 2011 Aug 1;19(15):4421-36.

[3]. Ecteinascidin 770, a tetrahydroisoquinoline alkaloid, sensitizes human lung cancer cells to anoikis. Anticancer Res. 2013 Feb;33(2):505-12.

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]
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C40H42N4O10S
Molecular Weight
770.84700
Exact Mass
770.262
CAS #
114899-80-8
PubChem CID
10952807
Appearance
White to off-white solid powder
Source
Ecteinascidia thurstoni and Ecteinascidia turbinata
LogP
4.191
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
15
Rotatable Bond Count
4
Heavy Atom Count
55
Complexity
1550
Defined Atom Stereocenter Count
7
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
InChi Key
BGFXHQYUWCGGLL-QWIBJBKUSA-N
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
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
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;
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO : ~50 mg/mL (~64.86 mM)
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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

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.

Contact Us