| Size | Price | |
|---|---|---|
| 500mg | ||
| Other Sizes |
Purity: ≥98%
Edotecarin (formerly ED-749; J-107088; J 107088; PF 804950) is a novel and potent inhibitor of topoisomerase I that can induces single-strand DNA cleavage with IC50 of 50 nM. The novel indolocarbazole edotecarin differs from other topoisomerase I inhibitors both pharmacokinetically and pharmacodynamically. In vitro, it is more potent than camptothecins and has a variable cytotoxic activity in 31 different human cancer cell lines. Edotecarin also possesses greater than additive inhibitory effects on cell proliferation when used in combination with other agents tested in vitro against various cancer cell lines. The present in vivo studies were done to extend the in vitro findings to characterize the antitumor effects of edotecarin when used either alone or in combination with other agents (i.e., 5-fluorouracil, irinotecan, cisplatin, oxaliplatin, and SU11248) in the HCT-116 human colon cancer xenograft model. Treatment effects were based on the delay in onset of an exponential growth of tumors in drug-treated versus vehicle control-treated groups. In all studies, edotecarin was active both as a single agent and in combination with other agents. Combination therapy resulted in greater than additive effects, the extent of which depended on the specific dosage regimen. Toxicity in these experiments was minimal. Of all 359 treated mice, the six that died of toxicity were in the high-dose edotecarin/oxaliplatin group. The results suggest that edotecarin may serve as effective chemotherapy of colon cancer when used as a single agent, in combination with standard regimens and other topoisomerase inhibitors or with novel agents, such as the multitargeted tyrosine kinase inhibitor SU11248.
| ln Vitro |
Edocalin (0.6 μmol/L) enhances DNA-protein complex formation in human colon cancer cells labeled with 3H thymidine in a time-dependent manner [1].
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|---|---|
| ln Vivo |
Edotecarin exhibits potent anti-metastatic properties and can enhance the survival rate of mice with intracranial D-456MG glioma by 83% [1]. Tumor growth was delayed by edocaline for a period of time that varied from 10.45 days at the lowest dose (3 mg/kg) to 24.83 days at the maximum dose (100 mg/kg). When edocalin and irinotecan are used in combination, the anticancer activity in vivo is enhanced as compared to when they are used alone [2].
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Edocarin does not form active metabolites and is not a substrate for P450-mediated metabolism in vitro. Biological Half-Life 20 to 25 hours |
| References | |
| Additional Infomation |
Edocaline is a novel non-camptothecin-based DNA topoisomerase I inhibitor, belonging to the indolecarbazole class of compounds. Edocaline is a synthetic indolecarbazole compound with antitumor activity. Edocaline inhibits topoisomerase I by stabilizing the DNA-enzyme complex and enhancing single-stranded DNA cleavage, thereby inhibiting DNA replication and reducing tumor cell proliferation. (NCI04)
Drug Indications Clinical studies of edocaline have shown its effectiveness in patients with colorectal cancer, esophageal cancer, and other solid tumors. Mechanism of Action Edocaline inhibits topoisomerase I by stabilizing the DNA-enzyme complex and enhancing single-stranded DNA breakage, thereby inhibiting DNA replication and reducing tumor cell proliferation. Pharmacodynamics Edocaline (formerly known as J-107088) is a novel non-camptothecin-based DNA topoisomerase I inhibitor. It belongs to the indolecarbazole class of compounds. Compared to NB-506 or camptothecin (CPT), edocaline is a novel topoisomerase I inhibitor that more effectively induces single-strand DNA breaks and acts on different DNA sequences. The DNA-topoisomerase I complex induced by edocaline is more stable than that induced by CPT or NB-506. Compared to other topoisomerase I inhibitors, edocaline's antitumor activity is less dependent on the cell cycle. Edocaline is an indolecarbazole compound with a structure related to astrosaporin but lacks protein kinase inhibitory activity. The antitumor activity of edocaline has been tested in vitro and in vivo, and tumor growth inhibition has been observed in models of breast cancer, cervical cancer, pharyngeal cancer, lung cancer, prostate cancer, colon cancer, gastric cancer, and liver cancer. Edocaline is effective against cells that have acquired P-glycoprotein-related resistance. In vitro experiments have shown that edocalin has a synergistic effect when used in combination with cisplatin, 5-fluorouracil, etoposide, paclitaxel, doxorubicin, vincristine, CPT and gemcitabine. |
| Molecular Formula |
C29H28N4O11
|
|---|---|
| Molecular Weight |
608.55282
|
| Exact Mass |
608.175
|
| CAS # |
174402-32-5
|
| PubChem CID |
9808998
|
| Appearance |
Yellow to orange solid powder
|
| Density |
1.96g/cm3
|
| Boiling Point |
1047.5ºC at 760 mmHg
|
| Flash Point |
587.3ºC
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| Vapour Pressure |
0mmHg at 25°C
|
| Index of Refraction |
1.886
|
| LogP |
-0.7
|
| Hydrogen Bond Donor Count |
10
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
44
|
| Complexity |
1120
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
C1=CC2=C(C=C1O)NC3=C4C(=C5C(=C23)C(=O)N(C5=O)NC(CO)CO)C6=C(N4[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)CO)O)O)O)C=C(C=C6)O
|
| InChi Key |
QMVPQBFHUJZJCS-NTKFZFFISA-N
|
| InChi Code |
InChI=1S/C29H28N4O11/c34-7-10(8-35)31-33-27(42)20-18-13-3-1-11(37)5-15(13)30-22(18)23-19(21(20)28(33)43)14-4-2-12(38)6-16(14)32(23)29-26(41)25(40)24(39)17(9-36)44-29/h1-6,10,17,24-26,29-31,34-41H,7-9H2/t17-,24-,25+,26-,29-/m1/s1
|
| Chemical Name |
6-((1,3-dihydroxypropan-2-yl)amino)-2,10-dihydroxy-12-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione
|
| Synonyms |
PHA782615; J107088; ED749; PHA-782615; J-107088; ED-749; PHA 782615; J 107088; ED 749.
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6433 mL | 8.2163 mL | 16.4325 mL | |
| 5 mM | 0.3287 mL | 1.6433 mL | 3.2865 mL | |
| 10 mM | 0.1643 mL | 0.8216 mL | 1.6433 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.
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