| Size | Price | |
|---|---|---|
| 25mg | ||
| 50mg | ||
| 100mg | ||
| Other Sizes |
| Targets |
Bcr-Abl; NF-κB; CaMKII
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|---|---|
| ln Vitro |
Previous studies showed that the natural compound berbamine, from Chinese herb Berberis amurensis, selectively induces apoptosis of imatinib (IM)-resistant-Bcr/Abl-expressing leukemia cells from the K562 cell line and CML patients. Here, a series of new berbamine derivatives were obtained by synthesis. In this series, high to very high activity in vitro has been found. Compounds 2e, 2g, 3f, 3k, 3q and 3u exhibited consistent high anti-tumor activity for imatinib-resistant K562 leukemia cells. Their IC(50) values at 48h were 0.36-0.55 microM, whereas berbamine IC(50) value was 8.9 microM. Cell cycle analysis results showed that compound 3h could reduce G0/G1 cells. In particular, these compounds displayed potent inhibition of the cytoplasm-to-nucleus translocation of NF-kappaB p65 which plays a critical role in the survival of leukemia stem cells. These results suggest that berbamine could be a good starting point for the development of novel lead compounds in the fight against leukemia.[1]
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| Cell Assay |
Cell line, culture conditions, and growth assays [1]
Human chronic myeloid leukemia cell line imatinib-resistant-K562 (K562-R), which constitutively express endogenous p210Bcr/Abl oncoprotein, were grown in RPMI-1640 medium supplemented with 10% fetal calf serum (FCS), 100 units/ml penicillin G, and 100 μg/ml streptomycin at 37 °C in a 95% air, 5% CO2 humidified incubator. K562-R cells expresse multipledrug resistance-1(MDR1) and are highly resistant to IM and conventional chemotherapeutic agents. Cell number and viabilities were monitored by hemocytomer and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. Detection of NF-κB p65 proteins [1] Leukemia cells were treated with berbamine (8 μg/ml) or berbamine derivatives (0.5 μg/ml), and total and nuclear cellular proteins were extracted using the Mammalian Protein Extraction Reagent (Pierce). NF-κB p65 protein was detected using Western blot. Flow cytometry [1] K562-R cells at a density of 2 × 105 cells/mL were treated with various concentrations of compound 3h (1.0 μg/ml, 2.0 μg/ml) for 48 h. The cells were harvested, washed with PBS and centrifuged. The fixation of cells was relized through the addition of 4 ml ethanol (70% ice-cold) and then keeping cells at 4 °C overnight until DNA staining. The fixed cells were treated with 100 μg/ml Rnase A in PBS for 1 h, followed by staining with 50 μg/ml propidium iodide in PBS in the dark. The DNA content of eukaryotic cells was then measured with flow cytometery. |
| Toxicity/Toxicokinetics |
The intraperitoneal LD50 in rats was 500 mg/kg, according to the National Academy of Sciences, National Research Council and Coordinating Center for Chemistry and Biology, 5(26), 1953; the oral LD50 in mice was 1700 mg/kg, according to Chinese Traditional and Herbal Drugs, 14(45), 1983; the intraperitoneal LD50 in mice was 75 mg/kg, according to the Chinese Journal of Chemistry and Pharmaceutical Sciences, 24(2413), 1976 [PMID:1017086]; the intravenous LD50 in mice was 17430 μg/kg, according to Chinese Traditional and Herbal Drugs, 14(45), 1983.
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| References | |
| Additional Infomation |
series of berberine derivatives were synthesized, and their antileukemic activity against the imatinib-resistant K562 leukemia cell line was evaluated. Etherification, esterification, or sulfonation of the phenolic hydroxyl group of berberine significantly enhanced its cytotoxic activity against leukemia cell lines. Most compounds exhibited potent cytotoxic activity in the micromolar concentration range. Compounds 2e, 2g, 3f, 3k, 3q, and 3u showed the best activity with IC50 values of 0.36 μM, 0.40 μM, 0.55 μM, 0.40 μM, 0.50 μM, and 0.46 μM, respectively. Notably, these compounds also exhibited potent inhibition of NF-κB p65 cytoplasmic to nuclear translocation, which is crucial for the survival of leukemia stem cells. Cell cycle analysis of the K562-R cell line showed that these compounds reduced quiescent (G0/G1 phase) cells, suggesting that berberine derivatives may have the potential to kill leukemia stem cells. [1]
|
| Molecular Formula |
C39H42N2O7
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|---|---|
| Molecular Weight |
650.76
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| Exact Mass |
650.299
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| CAS # |
73885-53-7
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| Related CAS # |
E6 Berbamine(Berbamine p-nitrobenzoate;114784-59-7;Berbamine;478-61-5;Berbamine dihydrochloride;6078-17-7;Berbamine acetate;73885-53-7;Berberine;2086-83-1;Berberine sulfate;633-66-9
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| PubChem CID |
287690
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
725.9±60.0 °C at 760 mmHg
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| Flash Point |
392.8±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.586
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| LogP |
3.83
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
48
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| Complexity |
1070
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)OC1=C2C=C(CC3C4=C(C(=C(C=C4CCN3C)OC)OC)OC5=C(C=C6CCN(C(C6=C5)CC7=CC=C(O2)C=C7)C)OC)C=C1
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| InChi Key |
QQHBFLLFMBTZBU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C39H42N2O7/c1-23(42)46-32-12-9-25-18-31-37-27(14-16-41(31)3)21-36(44-5)38(45-6)39(37)48-35-22-29-26(20-33(35)43-4)13-15-40(2)30(29)17-24-7-10-28(11-8-24)47-34(32)19-25/h7-12,19-22,30-31H,13-18H2,1-6H3
|
| Chemical Name |
(20,21,25-trimethoxy-15,30-dimethyl-7,23-dioxa-15,30-diazaheptacyclo[22.6.2.23,6.18,12.114,18.027,31.022,33]hexatriaconta-3(36),4,6(35),8,10,12(34),18,20,22(33),24,26,31-dodecaen-9-yl) acetate
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| Synonyms |
73885-53-7; 6,6',7-trimethoxy-2,2'-dimethylberbaman-12-yl acetate; (20,21,25-trimethoxy-15,30-dimethyl-7,23-dioxa-15,30-diazaheptacyclo[22.6.2.23,6.18,12.114,18.027,31.022,33]hexatriaconta-3(36),4,6(35),8,10,12(34),18,20,22(33),24,26,31-dodecaen-9-yl) acetate; NSC147754; BERBAMINE E6; SCHEMBL16192541; DTXSID00995023; C44H43N3O9;
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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 |
| 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) |
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 | 1.5367 mL | 7.6833 mL | 15.3666 mL | |
| 5 mM | 0.3073 mL | 1.5367 mL | 3.0733 mL | |
| 10 mM | 0.1537 mL | 0.7683 mL | 1.5367 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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