| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
TDP1 (tyrosyl-DNA phosphodiesterase 1). TDP1 is a DNA repair enzyme that removes covalent topoisomerase I-DNA adducts. By inhibiting TDP1, this compound prevents the repair of topoisomerase I-mediated DNA damage, leading to the accumulation of DNA strand breaks and enhanced cytotoxicity in cancer cells.
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| ln Vitro |
TDP1 Inhibitor-1 inhibits TDP1 enzymatic activity with an IC₅0 of 7 microM. The compound shows cytotoxicity against multiple cancer cell lines. By blocking TDP1-mediated DNA repair, it enhances the efficacy of topoisomerase I poisons (such as camptothecin and its derivatives) by preventing the resolution of drug-induced DNA cleavage complexes.
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| ln Vivo |
TDP1 Inhibitor-1 is expected to demonstrate antitumor activity in vivo, particularly in combination with topoisomerase I inhibitors. By preventing TDP1-mediated DNA repair, the compound sensitizes tumors to topoisomerase I poisons, leading to enhanced DNA damage and tumor cell death. Efficacy would be assessed in xenograft models using combination therapy approaches.
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| Enzyme Assay |
TDP1 enzymatic activity is measured using a fluorogenic or radiometric assay. A synthetic DNA substrate containing a covalently linked tyrosine residue (mimicking the topoisomerase I-DNA adduct) is incubated with recombinant TDP1 enzyme and serial dilutions of test compound. The release of the tyrosine moiety is quantified, and IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Cancer cell lines (e.g., colorectal, ovarian, or lung cancer cells) are treated with TDP1 Inhibitor-1 alone or in combination with topoisomerase I inhibitors (e.g., camptothecin, irinotecan, or topotecan). Cell viability is assessed using MTT or CellTiter-Glo assays. DNA damage is measured by gamma-H2AX foci formation or comet assay. Cytotoxicity enhancement is calculated as the combination index.
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| Animal Protocol |
Mice bearing subcutaneous tumor xenografts are treated with TDP1 Inhibitor-1 alone or in combination with a topoisomerase I inhibitor. Tumor growth is monitored, and tumors are harvested for pharmacodynamic analysis of DNA damage markers (gamma-H2AX) and apoptosis. Efficacy is determined by tumor growth inhibition and survival.
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| ADME/Pharmacokinetics |
The compound has a molecular weight of 446.49 g/mol and formula C2₆H2₆N2O₅. Standard PK parameters (half-life, Cmax, AUC, clearance, volume of distribution, oral bioavailability) would be determined in rodent PK studies following IV and PO administration. The compound is formulated in suitable vehicles for in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicology data for TDP1 Inhibitor-1 are not publicly available. Standard preclinical safety assessment would include cytotoxicity profiling, hERG inhibition testing, and repeat-dose toxicology studies in rodents. Given its mechanism of inhibiting DNA repair, combination toxicology with topoisomerase I inhibitors would be particularly relevant.
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| References | |
| Additional Infomation |
TDP1 Inhibitor-1 is a research compound for cancer studies. It is not clinically approved. The compound is useful for studying TDP1 biology and developing combination therapies with topoisomerase I inhibitors to overcome drug resistance. TDP1 inhibition represents a promising strategy for enhancing the efficacy of existing chemotherapeutic agents.
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| Molecular Formula |
C26H26N2O5
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|---|---|
| Molecular Weight |
446.50
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| Exact Mass |
446.184
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| CAS # |
2248702-80-7
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| PubChem CID |
138454772
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
661
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1COC2C1=CC1=C(C3N=C(C4C(=CC(OC)=C(C=4)OC)C=3C=C1)OCCN1CCCC1)C=2
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| InChi Key |
AXNFOXAWCCNLFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H26N2O5/c1-29-21-13-19-17-6-5-16-11-23-24(33-15-32-23)12-18(16)25(17)27-26(20(19)14-22(21)30-2)31-10-9-28-7-3-4-8-28/h5-6,11-14H,3-4,7-10,15H2,1-2H3
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| Chemical Name |
2,3-dimethoxy-13-(2-pyrrolidin-1-ylethoxy)-[1,3]benzodioxolo[5,6-c]phenanthridine
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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) |
DMSO : ~3.33 mg/mL (~7.46 mM)
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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 | 2.2396 mL | 11.1982 mL | 22.3964 mL | |
| 5 mM | 0.4479 mL | 2.2396 mL | 4.4793 mL | |
| 10 mM | 0.2240 mL | 1.1198 mL | 2.2396 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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