| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Topoisomerase II (topo II) – stabilizes topoisomerase II-DNA cleavable complex, inhibits topoisomerase II activity [1][2][3]
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|---|---|
| ln Vitro |
In Vitro: Amrubicin (20 μM for 1 h) induced cell cycle arrest at G₂/M phase in human leukemia U937 cells, increased sub-G₁ phase cells (apoptotic population), and induced typical apoptosis with nuclear condensation, fragmentation (Hoechst 33258 staining), and internucleosomal DNA fragmentation (agarose gel electrophoresis). These effects were inhibited by the topoisomerase II catalytic inhibitor ICRF-193 (1 μM). [3]
Amrubicin induced apoptosis in U937 cells in a dose-dependent manner with IC50 of 5.6 μM (1 h exposure). [3] Amrubicin (20 μM for 1 h) induced reduction in mitochondrial membrane potential (ΔΨm) in U937 cells, with maximal reduction at 3-6 h. [3] Amrubicin (20 μM for 1 h) activated caspase-3/7 (DEVD-specific cleavage) in U937 cells at 2-4 h, but did not activate caspase-1 (YVAD-specific cleavage). [3] In A549 human lung adenocarcinoma cells, amrubicin (2.5 μg/ml for 3 h) enhanced radiosensitivity when administered prior to X-ray irradiation, reducing the shoulder-shaped portion of the survival curve (indicating inhibition of sublethal damage repair). The D₀ value for irradiation alone was 2.0 Gy; with amrubicin pre-treatment, D₀ was 1.7 Gy (enhancement ratio 1.38). [1] In A549 cells, amrubicin (2.5 μg/ml for 3 h) prior to fractionated irradiation (2 Gy × 4 fractions, 24 h intervals) reduced surviving fraction from 0.19 (irradiation alone) to 0.0093. [1] Amrubicin (20 μM for 1 h) induced DNA fragmentation in U937 cells, which was inhibited by ICRF-193 (1 μM). [3] In human cancer cell lines (LX-1, A431, BT-474, A549), amrubicin showed antiproliferative activity with IC50 values ranging from 0.61-3.0 μg/ml. [2] |
| ln Vivo |
In Vivo: In human lung cancer xenograft models (athymic nude mice), amrubicin (25 mg/kg, i.v., single dose on day 0) significantly inhibited tumor growth in SCLC (Lu-24: T/C = 17%; Lu-134: T/C = 9%) and NSCLC (Lu-99: T/C = 29%; LC-6: T/C = 50%; L-27: T/C = 26%). Doxorubicin (12.5 mg/kg) was effective against Lu-24 but not Lu-134. Body weight decrease was within 10% in all treatment groups. [2]
In combination studies, amrubicin (25 mg/kg i.v.) enhanced the antitumor activity of cisplatin (10 mg/kg i.v.) against LX-1 tumors (T/C: amrubicin alone 57%, combination 31%); irinotecan (120 mg/kg i.v.) (T/C: amrubicin alone 41%, combination 24%); vinorelbine (16 mg/kg i.p.) against QG-56 tumors (T/C: amrubicin alone 43%, combination 27%); tegafur/uracil (28 mg/kg p.o., 5qd) against SC-6 tumors (T/C: amrubicin alone 8.5%, combination 3.7%); trastuzumab (100 mg/kg i.p., twice weekly × 2 weeks) against 4-1ST tumors (T/C: amrubicin alone 8.8%, combination 1.6%). Gemcitabine combination did not significantly enhance efficacy compared to amrubicin alone. [2] In A549 cells, amrubicin (2.5 μg/ml for 3 h) prior to X-ray irradiation enhanced radiosensitivity in a fractionated irradiation protocol (2 Gy × 4 fractions, 24 h intervals). [1] |
| Enzyme Assay |
No detailed enzyme activity assays (e.g., purified topoisomerase II activity, SPR, ITC, HTRF) were described for amrubicin in these papers. Topoisomerase II-mediated DNA cleavage was inferred from cellular DNA fragmentation studies inhibited by ICRF-193. [2][3]
|
| Cell Assay |
U937 human leukemia cells were cultured in RPMI-1640 with 10% FBS. Cells were treated with amrubicin (20 μM for 1 h), washed, and incubated in drug-free medium. Cell cycle analysis: fixed in 80% ethanol, stained with propidium iodide (50 μg/ml) with RNase A, analyzed by flow cytometry. Apoptosis detection: Hoechst 33258 staining for nuclear morphology; DNA fragmentation on 2% agarose gel electrophoresis. [3]
A549 human lung adenocarcinoma cells were cultured in Eagle's MEM with NCTC-135, lactalbumin hydrolysate, and 15% newborn calf serum. Cells were treated with amrubicin (2.5 μg/ml for 3 h) prior to X-ray irradiation (130 kVp, 5 mA, 0.5 mm Al filter, 1.0 Gy/min). Colony formation assay: cells plated, incubated for 7-10 days, stained with crystal violet, colonies >50 cells counted. [1] Human cancer cell lines (LX-1, A431, BT-474, A549) were cultured in appropriate media. Cell proliferation assay: cells plated in 96-well plates, treated with serial dilutions of amrubicin for 3 days, viable cells measured using WST-1 or AlamarBlue. IC50 values determined. [2] |
| Animal Protocol |
Human tumor xenograft models: Female BALB/c nu/nu mice (6-8 weeks) were implanted s.c. with tumor fragments (~2-3 mm diameter) in the flank. When tumors reached 100-300 mm³, mice were randomized into groups (n=6-8). Amrubicin (25 mg/kg) was administered i.v. on day 0. For combination studies, amrubicin was given approximately 1 h before the other agent. Tumor diameters measured with calipers twice weekly; tumor volume calculated as (smaller diameter)² × (larger diameter)/2. T/C (%) = (mean tumor growth rate of treated group / mean tumor growth rate of control group) × 100. Body weight changes monitored. [2]
Radiosensitivity study: A549 cells treated with amrubicin (2.5 μg/ml) for 3 h prior to X-ray irradiation (0-8 Gy). For fractionated irradiation: 2 Gy per fraction, 24 h intervals, total 4 fractions. Colony formation assay performed after 7-10 days incubation. [1] |
| ADME/Pharmacokinetics |
Amrubicin is metabolized to its active 13-hydroxy metabolite, amrubicinol, mainly by carbonyl reductases. In tumor-bearing mice treated with amrubicin, amrubicinol was found to be a major metabolite in tumor tissue, with levels higher than those of doxorubicin in mice treated with doxorubicin. In contrast, levels of amrubicin and amrubicinol were lower than those of doxorubicin in several normal tissues, including the heart. A good correlation was found between the level of amrubicinol in the tumor and the efficacy of amrubicin in vivo. [2][3]
In rats and dogs, the concentrations of amrubicin or amrubicinol in the heart afte |
| Toxicity/Toxicokinetics |
Amrubicin showed much less cardiotoxicity than doxorubicin in chronic experimental models using rabbits and dogs. [2]
In A549 cells, amrubicin (2.5 μg/ml) alone for 3 h had minimal cytotoxicity (surviving fraction ~0.9). [1] In human leukemia U937 cells, amrubicin (20 μM for 1 h) induced apoptosis as measured by sub-G₁ population increase. [3] In vivo, amrubicin (25 mg/kg i.v.) was well tolerated with body weight decrease within 10% in all treatment groups. [2] |
| References |
|
| Additional Infomation |
Amrubicin (amrubicin hydrochloride) is a completely synthetic 9-aminoanthracycline derivative characterized by a 9-amino group and a simple sugar moiety. It was developed to reduce cardiotoxicity while maintaining antitumor efficacy. Amrubicin is currently approved in Japan for the treatment of small-cell lung cancer and non-small-cell lung cancer. Its active metabolite, amrubicinol (13-hydroxy metabolite), is 5-100 times more active than amrubicin in inhibiting human tumor cell growth. The selective distribution of amrubicinol in tumors (higher than in normal tissues including heart) contributes to the greater efficacy and lower cardiotoxicity of amrubicin compared to doxorubicin. [2][3]
Amurubicin hydrochloride is the hydrochloride salt of a third-generation synthetic 9-aminoanthracycline antitumor drug. Amurubicin intercalates into DNA and inhibits the activity of topoisomerase II, thereby suppressing DNA replication and the synthesis of RNA and proteins, ultimately leading to cell growth inhibition and cell death. This drug has shown higher antitumor activity than conventional anthracyclines and has not exhibited the cumulative cardiotoxicity common in this class of compounds. |
| Molecular Formula |
C25H25NO9.HCL
|
|---|---|
| Molecular Weight |
519.92824
|
| Exact Mass |
519.13
|
| CAS # |
110311-30-3
|
| Related CAS # |
92395-36-3 (HCl);110267-81-7;110311-30-3;
|
| PubChem CID |
114897
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
717.8ºC at 760 mmHg
|
| Flash Point |
387.9ºC
|
| Vapour Pressure |
1.26E-21mmHg at 25°C
|
| LogP |
2.134
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
36
|
| Complexity |
881
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
CC([C@@](C1)(N)C[C@H](O[C@@H]2OC[C@@H](O)[C@@H](O)C2)C(C1=C3O)=C(O)C4=C3C(C5=CC=CC=C5C4=O)=O)=O.Cl
|
| InChi Key |
BHMLHEQFWVQAJS-IITOGVPQSA-N
|
| InChi Code |
InChI=1S/C25H25NO9.ClH/c1-10(27)25(26)7-13-18(16(8-25)35-17-6-14(28)15(29)9-34-17)24(33)20-19(23(13)32)21(30)11-4-2-3-5-12(11)22(20)31;/h2-5,14-17,28-29,32-33H,6-9,26H2,1H3;1H/t14-,15+,16-,17-,25-;/m0./s1
|
| Chemical Name |
(7S,9S)-9-acetyl-9-amino-7-[(2S,4S,5R)-4,5-dihydroxyoxan-2-yl]oxy-6,11-dihydroxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride
|
| Synonyms |
SM-5887; SM 5887;
|
| 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
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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 | 1.9233 mL | 9.6167 mL | 19.2334 mL | |
| 5 mM | 0.3847 mL | 1.9233 mL | 3.8467 mL | |
| 10 mM | 0.1923 mL | 0.9617 mL | 1.9233 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.
Phase II trial of amrubicin and cisplatin chemotherapy for invasive thymoma
CTID: UMIN000003933
Phase: Phase II Status: Complete: follow-up complete
Date: 2010-08-01
Products are for research use only; We do not sell to patients
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