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100mg | ||
250mg | ||
500mg |
ln Vitro |
Voreloxin is a novel class of topoisomerase II poison and inhibitor that inserts into DNA to cause apoptosis, G2 arrest, and site-specific DNA DSBs. In CCRF-CEM cells, voreloxin (0.1–20 µM) causes site-selective DNA double-strand breaks and inhibits topoisomerase II activity. In part through topoisomerase II, voreloxin (0.11, 0.33, 1, 3 µM) promotes G2 arrest in the A549 lung cancer cell line. DNA intercalation is necessary for voreloxin's cytotoxic action. Nevertheless, Voreloxin (1–9 µM) does not generate a noticeable amount of ROS [1]. In AML cell lines MV4-11 and HL-60, voreloxin has strong cytotoxic action, with IC50 values of 95 ± 8 nM and 884 ± 114 nM, respectively. In acute leukemia cell lines, voreloxin with cytarabine exhibited additive or synergistic action [2]. With a mean LD50 of 2.3 μM, voreloxin exhibits activity against primary acute myeloid leukemia (AML). In the myeloid cell lines NB4 and HL-60, voreloxin has an LD50 of 0.59 μM ± 0.25 μM. Voreloxin acts on topoisomerase II and induces cell accumulation in the S and G2 phases of the cell cycle [3].
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ln Vivo |
When injected twice every four days (q4d × 2), voreloxin (20 mg/kg, i.v.) caused an 80% drop in bone marrow cells in CD-1 mice. Mice were given 10 mg/kg voreloxin and cytarabine at the same time to cause bone marrow ablation, sinusoidal dilatation, and adipocyte infiltration. In CD-1 mouse bone marrow and peripheral blood, voreloxin (20 mg/kg, i.v.) and cytarabine induce a reversible decrease in myeloid cells and lymphocytes. Combining voreloxin (10 mg/kg, q4d ×2) and cytarabine results in reversible neutropenia; platelet CD-1 mice are less affected [2].
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References |
[1]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8. [3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9 |
Molecular Formula |
C18H19N5O4S
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Molecular Weight |
401.44
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Exact Mass |
401.11577
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CAS # |
175414-77-4
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Related CAS # |
Voreloxin Hydrochloride;175519-16-1
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SMILES |
O=C(C1=CN(C2=NC=CS2)C3=C(C=CC(N4C[C@H](OC)[C@@H](NC)C4)=N3)C1=O)O
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Synonyms |
SNS-595; SNS595; SNS 595
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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 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.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4910 mL | 12.4552 mL | 24.9103 mL | |
5 mM | 0.4982 mL | 2.4910 mL | 4.9821 mL | |
10 mM | 0.2491 mL | 1.2455 mL | 2.4910 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.