| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
- ABCB1 (IC50=32 nM);
- ABCG2 (IC50=19 nM) |
|---|---|
| ln Vitro |
- Cytotoxicity：N,N-Dimethyl-idarubicin-trisaccharide shows excellent cytotoxicity against ABCG2-overexpressing and ABCB1-overexpressing cells with IC50s of 19 nM and 32 nM, respectively.
- Mechanism of action：The compound is an efficient DNA intercalating agent. The relevant structural changes do not reduce the DNA intercalation affinity of the compound or its targeting of topoisomerase IIα (topo IIα). It can specifically induce histone eviction without causing DNA double-strand breaks. |
| Cell Assay |
The specific experimental procedures are not described in detail in the literature. It only mentions that the cytotoxicity of the compound against wild-type K562 leukemia cells and ABCB1 - or ABCG2-overexpressing cells was detected, and the correlation with cytotoxicity was evaluated by comparing intracellular anthracycline levels and their subcellular localization.
|
| References | |
| Additional Infomation |
Anthracyclines are among the most effective anticancer drugs. Doxorubicin, daunorubicin, epirubicin, and idarubicin have been used clinically for decades, but their application remains hampered by treatment-related toxicity and resistance. We have previously demonstrated that DNA damage and histone removal induced by doxorubicin are drivers of its associated adverse reactions. However, it remains unclear whether these properties also determine resistance. In this study, we evaluated a library of 40 anthracycline drugs, examining their cytotoxicity, intracellular uptake, and subcellular localization in K562 wild-type cells and doxorubicin-resistant cells overexpressing the ABCB1 transporter. We screened several anthracyclines with potent cytotoxicity. Among them, N,N-dimethylidarubicin and anthracycline antibiotics (composed of idarubicin aglycone and acrabicin trisaccharide) stood out because they mediated cytotoxicity against doxorubicin-resistant cells through histone removal. Therefore, our findings reveal some under-studied anthracycline antibiotic variants that warrant further investigation in order to find safer and more effective anticancer drugs that can bypass ABCB1-mediated efflux. [1]
|
| Molecular Formula |
C40H49NO14
|
|---|---|
| Molecular Weight |
767.82
|
| Exact Mass |
767.315
|
| CAS # |
3033865-28-7
|
| PubChem CID |
172419483
|
| Appearance |
Typically exists as solids at room temperature
|
| Hydrogen Bond Donor Count |
4
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
55
|
| Complexity |
1460
|
| Defined Atom Stereocenter Count |
12
|
| SMILES |
C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=CC=CC=C5C4=O)O)(C(=O)C)O)N(C)C)O[C@H]6C[C@@H]([C@@H]([C@@H](O6)C)O[C@H]7CCC(=O)[C@@H](O7)C)O
|
| InChi Key |
IKSFXTURSYHHBK-RFGUSUBNSA-N
|
| InChi Code |
InChI=1S/C40H49NO14/c1-17-25(43)11-12-28(50-17)54-39-19(3)52-30(14-26(39)44)55-38-18(2)51-29(13-24(38)41(5)6)53-27-16-40(49,20(4)42)15-23-31(27)37(48)33-32(36(23)47)34(45)21-9-7-8-10-22(21)35(33)46/h7-10,17-19,24,26-30,38-39,44,47-49H,11-16H2,1-6H3/t17-,18-,19-,24-,26-,27-,28-,29-,30-,38+,39+,40-/m0/s1
|
| Chemical Name |
(7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-(dimethylamino)-5-[(2S,4S,5S,6S)-4-hydroxy-6-methyl-5-[(2R,6S)-6-methyl-5-oxooxan-2-yl]oxyoxan-2-yl]oxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione
|
| Synonyms |
N,N-Dimethyl-idarubicin-trisaccharide; 3033865-28-7; orb2664591; CHEMBL5434379;
|
| 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 |
| 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
|
|---|---|
| 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 | 1.3024 mL | 6.5119 mL | 13.0239 mL | |
| 5 mM | 0.2605 mL | 1.3024 mL | 2.6048 mL | |
| 10 mM | 0.1302 mL | 0.6512 mL | 1.3024 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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