Topobexin
Based on 1 Customer Validation
Topobexin is a TOP2B-selective inhibitor with IC50 values of 0.19 μM and 4.8 μM for TOP2B and TOP2A (DNA decatenation assay). Topobexin binds to non-homologous residues in the obex pocket and targets the ATPase domain of TOP2B. Topobexin prevents anthracycline-induced DNA double-strand break formation, apoptotic signaling mediated by caspase 3/7, 8 and 9, cardiomyocyte morphological changes, mitochondrial depolarization/loss, left ventricular systolic dysfunction, extracellular matrix remodeling, fibrotic alterations, and increases in plasma cardiac troponin T and BNP. Topobexin does not impair the antiproliferative effects of anthracyclines in cancer cells, exhibits no intrinsic cytotoxicity in cardiomyocytes, and is well tolerated in rabbits. Topobexin can be used in studies related to anthracycline-induced cardiotoxicity.
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- Pureté : 99.04%
- CAS No.: 3076446-44-8
- Formule: C29H35N3O4
- Masse moléculaire:489.61
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
topoisomerase II beta 0.19 μM (IC50) |
topoisomerase II alpha 4.8 μM (IC50) |
In Vitro
Topobexin (0.03-30 μM; 40 min) potently and selectively inhibits recombinant human TOP2B over TOP2A in a DNA decatenation assay, with an IC50 of 0.19 μM for TOP2B[1].
Topobexin (0.02-20 μM) selectively inhibits recombinant human TOP2B ATPase activity over TOP2A, with an IC50 of 0.35 μM for TOP2B and a selectivity ratio of 12[1].
Topobexin binds to the obex pocket of human TOP2A and TOP2B ATPase domains, with steric strain induced by the TOP2A-unique Y72 residue driving its preferential inhibition of TOP2B[1].
Topobexin (0.25-1 μM; 15 min) selectively inhibits and immobilizes YFP-TOP2B on DNA in HEK293F cells, without affecting YFP-TOP2A mobility[1].
Topobexin (10 μM; 3 hours) treatment of wild-type human induced pluripotent stem cell-derived cardiomyocytes partially phenocopies TOP2B gene inactivation, as evidenced by a significant positive correlation in transcriptomic changes between Topobexin-treated cells and TOP2B-knockout cardiomyocytes[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax |
|---|---|---|---|---|
| Rabbit[1] | 10 mg/kg | i.v. | 13.5 μM | 10 min |
In Vivo
Topobexin (10 mg/kg; i.v.; once weekly; 10 weeks) completely prevents chronic Daunorubicin-induced cardiotoxicity in rabbits, preserving LV systolic function, blocking cardiomyocyte damage and pathological myocardial remodeling, and improving survival[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:New Zealand White (male, 12-16 weeks old) (Anthracycline-induced cardiotoxicity)[1]
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Dosage:10 mg/kg
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Administration:i.v.; single 20 min infusion
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Result:Completely prevented the Daunorubicin-induced increase in left ventricular γH2AX, with levels comparable to saline-treated controls.
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Animal Model:New Zealand White (male, 12-16 weeks old) (Anthracycline-induced cardiotoxicity)[1]
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Dosage:10 mg/kg
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Administration:i.v.; once weekly; 10 weeks; 20 min infusion prior to each Daunorubicin dose
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Result:Ensured 100% survival to the scheduled end of the experiment, compared to one premature death in the Daunorubicin-only group.
Prevented Daunorubicin-induced decreases in left ventricular systolic function, with LV fractional shortening and LV dP/dt_max matching saline-treated controls.
Blocked Daunorubicin-induced elevations in plasma cardiac troponin T, LV BNP mRNA, and LV mRNA levels of fibronectin 1 and collagen I alpha1, with all markers comparable to saline controls.
Maintained body weight gain matching the Daunorubicin-only group, with no additional toxicity observed compared to saline controls.
Chemical Information
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CAS No. 3076446-44-8
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Appearance Solid
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Masse moléculaire 489.61
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Formule C29H35N3O4
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Color White to off-white
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SMILES
CCCC1=CC(OC2=C(C(OCCN3CCN(CC3)C)=CC=C12)C(N4CCCC5=C4C=CC=C5)=O)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 25 mg/mL (51.06 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
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Fibrosis/Collagen Morphometry
Fibrosis and collagen morphometry is based on the quantitative visualization of fibrillar collagen deposition in tissue sections using histochemical stains such as Sirius Red (Picrosirius Red) or Masson's trichrome, followed by image-based or polarization-enhanced analysis to estimate collagen proportional area as a surrogate of extracellular matrix accumulation during fibrotic remodeling. Sirius Red combined with polarized light microscopy enhances detection of collagen fibers due to birefringence properties, enabling more specific visualization of collagen type I and III fibrils compared to conventional bright-field histology, while whole-section or region-restricted digital morphometry reduces field-selection bias in fibrosis assessment. Alternative quantitative approaches include second harmonic generation (SHG) and two-photon excited fluorescence microscopy, which enable label-free detection of fibrillar collagen and have been validated against histological staining and biochemica
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Collagen: Sirius Red Staining
Sirius Red or picrosirius red staining is a histochemical method for visualizing collagen-rich extracellular matrix in tissue sections, and collagen fibers are detected as red-stained structures under bright-field microscopy with enhanced birefringence under polarized light. Picrosirius red is useful for assessing total collagen organization, distribution, and fibrosis burden, but polarized color should not be interpreted as a definitive collagen type I versus type III readout because color is affected by fiber orientation, thickness, and packing.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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Mitochondrial membrane-potential fluorescent assay
Mitochondrial membrane potential fluorescent assays estimate ΔΨm in living cells using lipophilic cationic dyes such as TMRM, TMRE, rhodamine 123, and JC-1, which accumulate in mitochondria according to membrane polarization; loss of signal after FCCP or CCCP treatment is interpreted as mitochondrial depolarization. TMRM/TMRE and rhodamine 123 are commonly used for semi-quantitative live-cell microscopy or flow cytometry, while JC-1 can report a shift from red aggregate fluorescence to green monomer fluorescence during depolarization; interpretation requires controls because dye concentration, quenching mode, cell type, dye efflux, and mitochondrial mass can affect fluorescence independently of ΔΨm.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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ECM-Embedded Organoid (Matrigel/Dome) Culture
ECM-embedded organoid dome culture embeds epithelial stem cells, crypts, organoid fragments, or tumor-derived epithelial cells in a basement-membrane-like hydrogel such as Matrigel, allowing 3D growth, self-organization, lumen formation, budding or cystic morphogenesis, and lineage maintenance under defined niche-factor-containing medium. The primary readouts are organoid establishment efficiency, growth, morphology, passaging capacity, lineage-marker expression, and, when fluorescently labeled lines are used, microscopy- or flow-cytometry-based quantification of population behavior in 3D culture.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Matrigel/ECM Transwell Invasion Assay
The Matrigel/ECM Transwell invasion assay measures the ability of cells to move toward a chemoattractant while crossing an extracellular-matrix barrier placed on a porous membrane; therefore, the readout reflects both chemotactic motility and matrix invasion rather than migration alone. Matrigel is a basement-membrane-rich matrix derived from Engelbreth-Holm-Swarm mouse sarcoma and has been used as a reconstituted basement membrane barrier in chemoinvasion assays. The assay readout is generated by quantifying cells that reach the underside of the insert membrane or lower compartment after incubation, commonly by staining and counting invaded cells or by fluorescence-based quantification.
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Matrigel Transwell/Boyden Chamber Invasion Assay
Matrigel Transwell/Boyden chamber invasion assay measures the ability of cells to degrade or traverse an extracellular matrix-coated porous membrane and move from an upper chamber toward a chemoattractant in a lower chamber. Invasion is distinguished from migration by coating the membrane with Matrigel or basement membrane matrix; uncoated inserts measure migration, while coated inserts require cells to cross an ECM barrier before reaching the underside of the membrane.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Pureté et documentation
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Fiche technique (280 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Kubeš J, et al. Topobexin targets the Topoisomerase II ATPase domain for beta isoform-selective inhibition and anthracycline cardioprotection. Nat Commun. 2025;16(1):4928. Published 2025 May 28. [Content Brief]
[2]. Kosić M, et al. Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection. Int J Mol Sci. 2025;26(20):10130. Published 2025 Oct 17. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0424 mL | 10.2122 mL | 20.4244 mL | 51.0611 mL |
| 5 mM | 0.4085 mL | 2.0424 mL | 4.0849 mL | 10.2122 mL | |
| 10 mM | 0.2042 mL | 1.0212 mL | 2.0424 mL | 5.1061 mL | |
| 15 mM | 0.1362 mL | 0.6808 mL | 1.3616 mL | 3.4041 mL | |
| 20 mM | 0.1021 mL | 0.5106 mL | 1.0212 mL | 2.5531 mL | |
| 25 mM | 0.0817 mL | 0.4085 mL | 0.8170 mL | 2.0424 mL | |
| 30 mM | 0.0681 mL | 0.3404 mL | 0.6808 mL | 1.7020 mL | |
| 40 mM | 0.0511 mL | 0.2553 mL | 0.5106 mL | 1.2765 mL | |
| 50 mM | 0.0408 mL | 0.2042 mL | 0.4085 mL | 1.0212 mL |
Topobexin Related Classifications
HY-174374 Related Classifications
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