| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
BNS-22 targets DNA topoisomerase II (TOP2), specifically both isoforms TOP2α and TOP2β. The compound is a catalytic inhibitor, meaning it inhibits the enzymatic activity of TOP2 without stabilizing the DNA-enzyme cleavage complex. This distinguishes it from TOP2 poisons (e.g., etoposide, doxorubicin) that trap the enzyme in a covalent complex with DNA, leading to DNA strand breaks and subsequent cell death. BNS-22 inhibits human TOP2α-mediated kinetoplast DNA decatenation with IC50 = 2.8 µM and TOP2β-mediated decatenation with IC50 = 0.42 µM. The compound does not induce DNA damage itself, as demonstrated by the absence of γ-H2AX induction, a marker of DNA double-strand breaks. In fact, BNS-22 exerts an antagonistic effect on DNA damage caused by TOP2 poisons, reducing etoposide-induced γ-H2AX expression. This unique mechanism may result in a different spectrum of biological effects and potentially lower genotoxicity compared to TOP2 poisons. The compound's antiproliferative activity is attributed to TOP2 inhibition leading to mitotic abnormalities and cell cycle disruption.
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| ln Vitro |
The human cervical epidermoid cancer cell line HeLa can have its cell proliferation inhibited and cell cycle progression affected in a dose-dependent manner by BNS-22 (0-30 μM, 24-48 h) [1]. BNS-22 (0-30 μM, 0-6 h) exerts an antagonistic impact on DNA damage caused by TOP2 toxin and does not cause DNA damage itself [1].
In vitro studies demonstrate that BNS-22 (0-30 µM, 24-48 h) inhibits cell proliferation and affects cell cycle progression in a dose-dependent manner in HeLa human cervical epidermoid cancer cells. The IC50 for cell growth inhibition after 24 hours is 4.9 µM, and after 48 hours is 1.0 µM. Cell cycle analysis shows that BNS-22 (0-30 µM, 24 h) increases the number of cells in G2/M phase, indicating cell cycle arrest. At 3 µM, BNS-22 disrupts mitotic spindle formation and induces polyploid cell formation. Western blot analysis reveals that BNS-22 (0-30 µM, 0-6 h) diminishes cellular TOP2β levels but does not affect TOP2α levels. Importantly, BNS-22 does not cause DNA damage itself, as shown by the absence of γ-H2AX induction, and it exerts an antagonistic effect on etoposide-induced decrease in γ-H2AX expression. These in vitro results establish BNS-22 as a catalytic TOP2 inhibitor with antiproliferative activity and a mechanism distinct from TOP2 poisons. |
| ln Vivo |
In vivo studies with BNS-22 are limited in publicly available literature. The compound's potent in vitro antiproliferative activity against human cancer cells and its unique mechanism as a catalytic TOP2 inhibitor suggest potential for in vivo antitumor efficacy, but specific in vivo studies (animal models, dosing regimens, tumor growth inhibition) have not been extensively reported. The compound's lack of DNA-damaging activity may translate to reduced toxicity in vivo compared to TOP2 poisons. BNS-22 induces mitotic abnormalities and has antiproliferative activity, characteristics that would be expected to translate to antitumor activity in vivo. However, comprehensive in vivo efficacy and toxicity data are needed to fully evaluate the compound's therapeutic potential. Researchers interested in in vivo applications should consult the primary literature for updated information and conduct appropriate studies to determine effective dosing and administration routes.
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| Enzyme Assay |
In vitro enzyme assays for TOP2 inhibition are performed using kinetoplast DNA decatenation assays. Human TOP2α or TOP2β is incubated with varying concentrations of BNS-22 and kinetoplast DNA (a catenated network of circular DNA molecules). The enzyme catalyzes the decatenation of kinetoplast DNA into individual minicircles, which can be resolved by agarose gel electrophoresis. Inhibition of decatenation is quantified by measuring the decrease in minicircle formation relative to control reactions. The IC50 values for BNS-22 are 2.8 µM for TOP2α and 0.42 µM for TOP2β. The assay demonstrates that BNS-22 is a catalytic inhibitor, as it inhibits the enzymatic activity without stabilizing the DNA-enzyme cleavage complex. This is confirmed by the absence of DNA damage in cellular assays (no γ-H2AX induction) and the antagonistic effect on etoposide-induced DNA damage. These enzyme assays are critical for characterizing the compound's potency, selectivity, and mechanism of action.
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| Cell Assay |
Cell proliferation experiment [1]
Cell Types: HeLa cell line Tested Concentrations: 0-30 μM Incubation Duration: 24 h, 48 h Experimental Results: Inhibited cell growth, the IC50 value after 24 hrs (hours) was 4.9 μM, and the IC50 value after 48 hrs (hours) was 1.0 μM. Cell cycle analysis[1] Cell Types: HeLa cell line Tested Concentrations: 0-30 μM Incubation Duration: 24 hrs (hours) Experimental Results: Increased number of cells in G2/M phase. 3 μM disrupts mitotic spindle formation and induces polyploid cell formation. Western Blot Analysis[1] Cell Types: HeLa cell line Tested Concentrations: 0-30 μM Incubation Duration: 0, 30 minutes, 1 hour, 2 hrs (hours), 4 hrs (hours), 6 hrs (hours) Experimental Results: Etoposide-induced decrease in γ-H2AX expression, Total expression diminished cellular TOP2β levels, but not TOP2α levels. In vitro cell-based assays with BNS-22 are conducted primarily in HeLa human cervical epidermoid cancer cells. Cell proliferation is assessed by treating cells with BNS-22 at concentrations ranging from 0-30 µM for 24 or 48 hours, followed by cell counting or metabolic activity assays (e.g., MTT). The IC50 for cell growth inhibition is 4.9 µM at 24 hours and 1.0 µM at 48 hours. Cell cycle analysis is performed by flow cytometry following propidium iodide staining of cells treated with BNS-22 (0-30 µM, 24 h); increased G2/M phase cells and polyploid cells are observed. Mitotic spindle formation is assessed by immunofluorescence staining of α-tubulin. Western blot analysis is used to assess TOP2α and TOP2β protein levels, γ-H2AX (DNA damage marker), and other relevant proteins following BNS-22 treatment (0-30 µM, 0-6 h). The absence of γ-H2AX induction confirms that BNS-22 does not cause DNA damage. These comprehensive cell-based assays characterize the compound's antiproliferative activity and mechanism of action. |
| Animal Protocol |
In vivo animal protocols for BNS-22 are not well-documented in publicly available literature. Based on the compound's in vitro activity, typical study designs for evaluating antitumor efficacy would involve administration of BNS-22 in rodent xenograft models bearing human tumor cells. Doses would be determined from in vitro potency data and preliminary toxicity assessments. Route of administration (oral, intraperitoneal, intravenous) would depend on the compound's solubility and bioavailability. Treatment duration and frequency would be optimized based on pharmacokinetic and pharmacodynamic data. Endpoints would include tumor growth inhibition, survival, histopathological analysis of tumors, and assessment of TOP2 inhibition in tumor tissues. Researchers should consult primary literature for updated protocols and conduct appropriate dose-finding and efficacy studies. The compound's lack of DNA-damaging activity may translate to a favorable safety profile, but this would need to be confirmed in vivo.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BNS-22 have not been extensively characterized in published literature. The compound has molecular weight 407.46, which is within the range typically associated with moderate oral bioavailability. The logP is 4.1, indicating moderate lipophilicity that may facilitate membrane permeability. The compound is soluble in DMSO at 2 mg/mL (warmed). For in vivo formulations, DMSO-based formulations can be prepared. Storage: powder at -20°C for 3 years, 4°C for 2 years; in solvent at -80°C for 6 months, -20°C for 1 month. Specific pharmacokinetic parameters such as half-life, Cmax, AUC, bioavailability, and tissue distribution have not been reported. Researchers planning in vivo studies should conduct appropriate pharmacokinetic studies to determine these parameters. The compound's physicochemical properties suggest it may have suitable characteristics for drug development, but empirical data are needed.
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| Toxicity/Toxicokinetics |
Toxicology data for BNS-22 are limited in publicly available sources. The compound's unique mechanism as a catalytic TOP2 inhibitor that does not induce DNA damage suggests potentially lower genotoxicity and reduced risk of secondary malignancies compared to TOP2 poisons (etoposide, doxorubicin) that cause DNA strand breaks. However, comprehensive toxicology studies (acute and chronic toxicity, genotoxicity, reproductive toxicity, cardiotoxicity) have not been reported. The compound has demonstrated antiproliferative activity against cancer cells, indicating potential for therapeutic applications, but safety profile needs to be established through systematic toxicology studies. The compound is for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling BNS-22. The compound should be stored properly and disposed of in accordance with applicable regulations. Researchers should consult the material safety data sheet (MSDS) for detailed safety information.
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| References | |
| Additional Infomation |
BNS-22 is a catalytic inhibitor of DNA topoisomerase II with CAS number 1151668-24-4, molecular formula C24H25NO5, and molecular weight 407.46. The compound is derived from the natural product GUT-70 isolated from the stem bark of Calophyllum brasiliense. BNS-22 inhibits human TOP2α with IC50 = 2.8 µM and TOP2β with IC50 = 0.42 µM. It is a catalytic inhibitor that does not induce DNA damage, distinguishing it from TOP2 poisons such as etoposide. The compound induces mitotic abnormalities and has antiproliferative activity. Purity is typically >98%. The compound is supplied as a solid and should be stored at room temperature. Solubility: DMSO 2 mg/mL (warmed). Synonyms: BNS-22. The compound is a valuable research tool for studying TOP2 biology, particularly the differences between catalytic inhibition and poisoning mechanisms. Not approved for clinical use; for research purposes only. The unique mechanism of BNS-22 makes it useful for investigating the role of TOP2 in cell division, DNA repair, and cancer, and for developing TOP2-targeted therapies with potentially reduced genotoxicity.
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| Molecular Formula |
C24H25NO5
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| Molecular Weight |
407.459007024765
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| Exact Mass |
407.173
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| CAS # |
1151668-24-4
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| PubChem CID |
25265819
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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 |
622.7±55.0 °C at 760 mmHg
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| Flash Point |
330.4±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.593
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
677
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C(C2=C3OC(=O)C=C(CCC)C3=C(OC)C=C2OC)=O)C2=C(C=CC=C2)CCC1
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| InChi Key |
LRPUQCTZOSTSGL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25NO5/c1-4-8-16-13-20(26)30-23-21(16)18(28-2)14-19(29-3)22(23)24(27)25-12-7-10-15-9-5-6-11-17(15)25/h5-6,9,11,13-14H,4,7-8,10,12H2,1-3H3
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| Chemical Name |
8-(3,4-dihydro-2H-quinoline-1-carbonyl)-5,7-dimethoxy-4-propylchromen-2-one
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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 | 2.4542 mL | 12.2711 mL | 24.5423 mL | |
| 5 mM | 0.4908 mL | 2.4542 mL | 4.9085 mL | |
| 10 mM | 0.2454 mL | 1.2271 mL | 2.4542 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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