| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
TDP1 (tyrosyl-DNA phosphodiesterase 1). TDP1 is a DNA repair enzyme that removes topoisomerase I-DNA cleavage complexes. TDP1 Inhibitor-2 is a potent TDP1 inhibitor (IC50=99 nM) that also inhibits the mutant SCAN1 TDP1 variant (IC50=3.5 microM). By inhibiting TDP1, the compound sensitizes cancer cells to Top1-targeting chemotherapy drugs like topotecan, blocking DNA repair and enhancing anti-cancer efficacy.
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|---|---|
| ln Vitro |
TDP1 Inhibitor-2 (Compound 5) exhibits strong anti-TDP1 activity, minimal cytotoxicity, and a synergistic effect with topotecan, a well-known Top1 anticancer agent [1].
TDP1 Inhibitor-2 shows potent anti-TDP1 activity in vitro with an IC50 of 99 nM, low cytotoxicity, and synergism with topotecan, a Top1 anticancer agent. When combined with topotecan, TDP1 Inhibitor-2 enhances the anti-proliferative effects of chemotherapy by preventing repair of topoisomerase I-mediated DNA damage. It has low cytotoxicity alone, suggesting a good safety profile when used in combination. |
| ln Vivo |
No in vivo activity data for TDP1 Inhibitor-2 are provided in the reference sources. As a TDP1 inhibitor designed to sensitize cancer cells to Top1 inhibitors, in vivo studies would likely involve xenograft mouse models with combination therapy of TDP1 Inhibitor-2 plus topotecan to evaluate tumor growth suppression and survival benefit.
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| Enzyme Assay |
Not explicitly detailed in reference sources. A typical TDP1 enzymatic assay involves incubating recombinant TDP1 with a fluorescent-labeled DNA substrate containing a phosphotyrosine bond, which mimics the topoisomerase I-DNA cleavage complex. TDP1 Inhibitor-2 is added at varying concentrations, and enzymatic activity is measured by release of fluorescent product over time at 37degC. IC50 is calculated from dose-response curves.
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| Cell Assay |
Not explicitly detailed in reference sources. A standard cytotoxicity assay for TDP1 Inhibitor-2 involves treating cancer cell lines with increasing concentrations of TDP1 Inhibitor-2 alone or in combination with topotecan for 72 hours, and cell viability is measured using MTT or clonogenic assay. Synergy is assessed by calculating combination index values. Low cytotoxicity of the inhibitor alone should be confirmed.
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| Animal Protocol |
No in vivo animal experimental protocols for TDP1 Inhibitor-2 are provided in the reference sources. A typical xenograft study would involve subcutaneous inoculation of cancer cells into nude mice. Once tumors reach a certain size, mice are treated with TDP1 Inhibitor-2 (e.g., orally or intraperitoneally) with or without topotecan for 2-4 weeks. Tumor volumes are measured every 2-3 days.
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| ADME/Pharmacokinetics |
TDP1 Inhibitor-2 has a molecular weight of 465.28 and formula C25H14Cl2O5. It is an organic compound that appears as a solid (white to yellow). Storage should be at -20degC as powder; in solution, it is stable at -80degC for 6 months or -20degC for 1 month. Solubility information is not detailed in the reference sources.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for TDP1 Inhibitor-2 are provided in the reference sources. The compound is reported to have low cytotoxicity in vitro when used alone, which is desirable for a chemosensitizing agent. However, comprehensive toxicity studies in animals would be required to assess safety for potential therapeutic use.
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| References | |
| Additional Infomation |
By inhibiting TDP1, a DNA repair enzyme that counteracts the effect of Top1 inhibitors, TDP1 Inhibitor-2 represents a promising chemosensitization strategy. It has shown in vitro synergy with topotecan, suggesting potential for enhancing the efficacy of existing chemotherapies. The compound is a research tool and not yet approved for clinical use.
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| Molecular Formula |
C25H14CL2O5
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|---|---|
| Molecular Weight |
465.281665325165
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| Exact Mass |
464.021
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| CAS # |
859142-95-3
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| PubChem CID |
1767837
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| Appearance |
White to yellow solid powder
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| LogP |
5.8
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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 |
4
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| Heavy Atom Count |
32
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| Complexity |
798
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)OC2=CC=CC=C2C=C1C1C2=CC=C(OCC3=C(Cl)C=CC=C3Cl)C=C2OC(=O)C=1
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| InChi Key |
QEOYHBDGERTIQV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H14Cl2O5/c26-20-5-3-6-21(27)19(20)13-30-15-8-9-16-17(12-24(28)31-23(16)11-15)18-10-14-4-1-2-7-22(14)32-25(18)29/h1-12H,13H2
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| Chemical Name |
7-[(2,6-dichlorophenyl)methoxy]-4-(2-oxochromen-3-yl)chromen-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) |
DMSO: ~8.3 mg/mL (~17.9 mM; with ultrasonication and warming by heating to 80°C)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 0.83 mg/mL (1.78 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (8.3 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1492 mL | 10.7462 mL | 21.4924 mL | |
| 5 mM | 0.4298 mL | 2.1492 mL | 4.2985 mL | |
| 10 mM | 0.2149 mL | 1.0746 mL | 2.1492 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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