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Purity: ≥98%
Daunorubicin HCl (Daunomycin; RP-13057; Rubidomycin; Ondena; Rubilem; DNM; DNR; DRB; FI6339; RP13057), the hydrochloride salt of daunorubicin, is an anthracycline analog and a topoisomerase II inhibitor which is approved for use as an antibiotic and chemotherapeutic drug.
| Targets |
Daunorubicins/Doxorubicins; Topoisomerase II
DNA topoisomerase II [1][2][4] |
|---|---|
| ln Vitro |
Daunorubicin hydrochloride (0-256 μg/mL, 30 min) inhibits the synthesis of DNA and RNA in Ehrlich ascites tumor cells, both sensitive and resistant[2].
Daunorubicin hydrochloride (7 nM-1.9 μM, 72 h) exhibits chemosensitivity in Molt-4 cells and L3.6 cells[3][4]. Daunorubicin hydrochloride (0.4 μM, 48 h) causes necrosis and apoptosis in L3.6 cells[4]. Daunorubicin hydrochloride (0.4 μM, 120 min) causes ROS generation in L3.6 cells[4]. Daunorubicin hydrochloride (2 μM, 24 h) induces autophagy in K562 cells (myeloid cell line)[6]. In sensitive Ehrlich ascites tumor cells, Daunorubicin HCl (Daunomycin) inhibited DNA and RNA synthesis in a concentration-dependent manner, with significant reduction in nucleic acid production at micromolar concentrations. Resistant cells showed less pronounced inhibition due to reduced drug accumulation [2] - In MOLT 4 human T-lymphoblastic leukemia cells, Daunorubicin HCl (Daunomycin) exhibited cytotoxicity, but the effect was attenuated in the presence of melanin, which reduced intracellular drug availability [3] - In human pancreatic carcinoma cells, Daunorubicin HCl (Daunomycin) alone induced both necrosis and apoptosis, characterized by cell membrane disruption, DNA fragmentation, and caspase activation. Combined with paclitaxel, it showed enhanced antitumor activity, with higher apoptotic and necrotic rates [4] - In acute myeloid leukemia (AML) cells, Daunorubicin HCl (Daunomycin) induced autophagy via reactive oxygen species (ROS) production and activation of autophagic signaling pathways. Overexpression of miR-15a-5p inhibited this autophagic response, conferring chemoresistance [6] - In Drosophila somatic cells, Daunorubicin HCl (Daunomycin) induced mutations and recombination events, indicating genotoxic activity associated with its topoisomerase II inhibition [1] |
| ln Vivo |
Daunorubicin hydrochloride (three intravenous injections at 48-hour intervals, at a dose of 3 mg/kg). causes rats to become nephrotoxic and cardiotoxic[5].
Daunorubicin hydrochloride (intraperitoneal injection, 10 mg/kg) causes sister chromatid exchanges in mice[7]. In daunorubicin-induced renal injury rat models, intravenous administration of Daunorubicin HCl (Daunomycin) at a single dose of 6.5 mg/kg caused progressive renal damage, characterized by increased serum creatinine and urea nitrogen levels, glomerular sclerosis, and tubular injury. This injury was associated with altered expression of angiotensin II and endothelin-1 receptors [5] |
| Enzyme Assay |
Inhibition of DNA and RNA synthesis by daunorubicin in sensitive and resistant Ehrlich ascites tumor cells in vitro [2].
DNA topoisomerase II activity assay: Purified DNA topoisomerase II was incubated with supercoiled plasmid DNA in reaction buffer. Daunorubicin HCl (Daunomycin) was added at serial concentrations, and the mixture was incubated at 37°C for 60 minutes. The reaction was terminated by adding SDS, and DNA products were separated by agarose gel electrophoresis. The inhibition of topoisomerase II-mediated DNA relaxation was assessed by quantifying the intensity of supercoiled DNA bands. Daunorubicin HCl (Daunomycin) was found to stabilize the enzyme-DNA cleavage complex, preventing DNA religation [1][2] |
| Cell Assay |
Cell Line: Molt-4 cells (a human T-lymphoblastic leukemia cell line), L3.6 cells (metastatic human pancreatic cell line)
Concentration: 7 nM-1.9 μM Incubation Time: 72 h Result: Inhibited cell viability with IC50 values of 40 nM (Molt-4) and 400 nM (L3.6). Nucleic acid synthesis inhibition assay: Sensitive and resistant Ehrlich ascites tumor cells were seeded in culture flasks and treated with Daunorubicin HCl (Daunomycin) at concentrations of 0.1-10 μM. Cells were labeled with radioactive precursors of DNA and RNA, and radioactivity incorporation was measured after 24 hours to evaluate nucleic acid synthesis rates [2] - Cytotoxicity assay with melanin: MOLT 4 cells were pre-incubated with melanin for 1 hour, then treated with Daunorubicin HCl (Daunomycin) at 0.5-5 μM for 48 hours. Cell viability was measured using a colorimetric assay, and the cytotoxicity ratio was calculated by comparing melanin-treated and non-treated cells [3] - Apoptosis and necrosis assay: Human pancreatic carcinoma cells were plated in 6-well plates and treated with Daunorubicin HCl (Daunomycin) (1-10 μM) alone or in combination with paclitaxel (0.1-1 μM). After 72 hours, cells were stained with annexin V-FITC and propidium iodide for flow cytometric analysis to distinguish apoptotic (annexin V-positive/PI-negative) and necrotic (annexin V-positive/PI-positive) cells. DNA fragmentation was detected by agarose gel electrophoresis [4] - Autophagy assay: AML cells were treated with Daunorubicin HCl (Daunomycin) at 1 μM for 24-48 hours. Autophagic flux was monitored by detecting LC3-II accumulation via western blot analysis. miR-15a-5p overexpression and knockdown experiments were performed to assess its effect on daunorubicin-induced autophagy [6] - Drosophila somatic mutation and recombination assay: Drosophila larvae were fed with medium containing Daunorubicin HCl (Daunomycin) at concentrations of 0.1-1 μg/mL. Adult flies were examined for wing hair mutations and recombination events to evaluate genotoxicity [1] |
| Animal Protocol |
Male Sprague-Dawley rats eight weeks of age are employed. Two more weeks are spent acclimating and keeping the animals in quarantine before the experiments begin. Day 0: A single intravenous injection of Daunorubicin (3 mg/kg) is given to each animal. To achieve an accumulative dose of 9 mg/kg, daunorubicin is given in three equal injections spaced 48 hours apart over the course of one week. It is well known that this dosage will cause nephrotoxicity and cardiotoxicity. As a control, age-matched rats (group Control; n=5) are injected with corresponding volumes of 0.9% NaCl. Twenty-two DNR-treated rats were split into two groups at random and given either a vehicle (group Daunorubicin; n = 12) or Telmisartan (10 mg/kg/day; group Daunorubicin+Telmisartan; n = 10). A prior report is used to determine the dosage of Telmisartan. Telmisartan is administered for 5 weeks after stopping Daunorubicin administration, commencing on the same day as Daunorubicin administration (6 weeks total). The length of the study was selected based on earlier reports. Rats are individually housed in metabolic cages on day 41, and urine samples are collected every 24 hours to measure protein concentrations and body weight (BW). Rats are sacrificed and kidney tissue is taken for semi-quantitative immunoblotting and immunohistochemical investigations after the six-week study period.
Rats known as Sprague-Dawley Renal injury model: Male Wistar rats were randomly divided into control and treatment groups (n=6 per group). Daunorubicin HCl (Daunomycin) was dissolved in sterile saline and administered as a single intravenous dose of 6.5 mg/kg via the tail vein. Control rats received an equal volume of sterile saline. Rats were sacrificed 4 weeks after administration, and blood samples were collected for serum creatinine and urea nitrogen measurement. Kidney tissues were harvested for histopathological examination and analysis of angiotensin II and endothelin-1 receptor expression [5] |
| Toxicity/Toxicokinetics |
Nephrotoxicity: Daunorubicin hydrochloride (daunorubicin) can induce dose-dependent kidney injury in rats, manifested as impaired renal function (elevated serum creatinine and blood urea nitrogen) and histological damage (glomerular sclerosis, tubular atrophy and interstitial fibrosis) [5] - Cytotoxicity: The drug exhibits concentration-dependent cytotoxicity in a variety of tumor cell lines, but its cytotoxicity is reduced in drug-resistant cells and melanin-treated MOLT 4 cells [2][3] - Genotoxicity: Daunorubicin hydrochloride (daunorubicin) can induce somatic mutations and recombination in Drosophila, indicating a potential genotoxic risk [1]
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| References |
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| Additional Infomation |
According to state or federal labeling requirements, daunorubicin hydrochloride may cause developmental toxicity.
Daunorubicin hydrochloride is an orange-red powder, appearing as slender red needle-like crystals, which decompose at 188-190 °C. It is an anticancer drug. Daunorubicin hydrochloride belongs to the anthracycline antibiotics. Daunorubicin hydrochloride is the hydrochloride salt of anthracycline antitumor antibiotics, and its therapeutic effect is similar to that of doxorubicin. Daunorubicin exerts cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair as well as the synthesis of RNA and proteins. Daunorubicin is a highly toxic anthracycline aminoglycoside antitumor drug, isolated from strains such as Streptomyces peucetius, and used to treat leukemia and other tumors. Daunorubicin hydrochloride (daunorubicin) is an anthracycline antibiotic with antitumor activity, widely used to treat hematologic malignancies such as acute myeloid leukemia[2][6]. - Mechanism of action: This drug exerts its anti-tumor effect by intercalating into DNA, inhibiting DNA topoisomerase II, inducing DNA strand breaks, and inhibiting DNA and RNA synthesis, ultimately leading to cell cycle arrest, apoptosis, and necrosis [1][2][4]. - Chemotherapy resistance: miR-15a-5p confers drug resistance to daunorubicin hydrochloride (daunorubicin) in acute myeloid leukemia (AML) cells by inhibiting drug-induced autophagy [6]. - Synergistic effect: When used in combination with paclitaxel, it can enhance the anti-tumor efficacy of daunorubicin hydrochloride (daunorubicin) in human pancreatic cancer cells by simultaneously inducing apoptosis and necrosis [4]. - Melanin interaction: Melanin binds to daunorubicin hydrochloride (daunorubicin), reducing its intracellular concentration and thus weakening its cytotoxicity [3]. |
| Molecular Formula |
C27H29NO10.HCL
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|---|---|
| Molecular Weight |
563.98
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| Exact Mass |
563.155
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| Elemental Analysis |
C, 57.50; H, 5.36; Cl, 6.29; N, 2.48; O, 28.37
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| CAS # |
23541-50-6
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| Related CAS # |
1884557-85-0; 20830-81-3; 371770-68-2 (citrate); 23541-50-6 (HCl)
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| PubChem CID |
62770
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| Appearance |
Red solid powder
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| Boiling Point |
770ºC at 760 mmHg
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| Melting Point |
188 - 190ºC
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| Flash Point |
419.5ºC
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| Vapour Pressure |
6.99E-26mmHg at 25°C
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| LogP |
2.531
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| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
39
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| Complexity |
960
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| Defined Atom Stereocenter Count |
6
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| SMILES |
Cl[H].O([C@@]1([H])C([H])([H])[C@@]([H])([C@@]([H])([C@]([H])(C([H])([H])[H])O1)O[H])N([H])[H])[C@]1([H])C2C(=C3C(C4C(=C([H])C([H])=C([H])C=4C(C3=C(C=2C([H])([H])[C@@](C(C([H])([H])[H])=O)(C1([H])[H])O[H])O[H])=O)OC([H])([H])[H])=O)O[H]
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| InChi Key |
GUGHGUXZJWAIAS-QQYBVWGSSA-N
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| InChi Code |
InChI=1S/C27H29NO10.ClH/c1-10-22(30)14(28)7-17(37-10)38-16-9-27(35,11(2)29)8-13-19(16)26(34)21-20(24(13)32)23(31)12-5-4-6-15(36-3)18(12)25(21)33;/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3;1H/t10-,14-,16-,17-,22+,27-;/m0./s1
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| Chemical Name |
(7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride
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| Synonyms |
Daunomycin HCl; RP 13057; Rubidomycin; RP-13057; RP13057; Daunomycin hydrochloride; daunomycin HCl; daunorubidomycine; US trade names: Cerubidine; Rubidomycin; Foreign brand names: Cerubidin; Daunoblastin; Daunoblastina; Ondena; Rubilem; Abbreviations: DNM; DNR; DRB; Code names: FI6339; RP13057
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: Saline: 30 mg/mL Solubility in Formulation 4: 33.33 mg/mL (59.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7731 mL | 8.8656 mL | 17.7311 mL | |
| 5 mM | 0.3546 mL | 1.7731 mL | 3.5462 mL | |
| 10 mM | 0.1773 mL | 0.8866 mL | 1.7731 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.
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations
CTID: NCT02883049
Phase: Phase 3 Status: Active, not recruiting
Date: 2024-11-13
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