| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Topoisomerase I
Topoisomerase I inhibitor 8 targets topoisomerase I, an enzyme that relieves torsional stress in DNA during replication and transcription by creating transient single-strand breaks. By binding to and stabilizing the topoisomerase I-DNA cleavage complex, the compound prevents the religation of the cleaved DNA strand, resulting in the accumulation of DNA breaks that trigger apoptosis. The compound's hexacyclic structure, related to camptothecin, allows for potent and selective inhibition of topoisomerase I over topoisomerase II, making it a valuable tool for studying topoisomerase I biology. |
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| ln Vitro |
Topoisomerase I inhibitor 8 (compound 57) exhibits anticancer activity against three cell line cultures, with IC50 values of 0.22 ng/mL (P388), 2.06 ng/mL (HOC-21), and 0.17 ng/mL (QG-56), in that order[1]. Topoisomerase I inhibitor 8 (IC50 of compound/IC50 of SN-38=0.51) causes DNA to transition from the supercoiled form to the relaxed form when topoisomerase I is present. It is more effective than SN-38 (HY-13704).
In vitro studies demonstrate that Topoisomerase I inhibitor 8 exhibits potent anticancer activity against multiple cancer cell lines. The compound shows IC₅0 values of 0.22 ng/mL (P388 murine leukemia), 2.06 ng/mL (HOC-21 human ovarian cancer), and 0.17 ng/mL (QG-56 human lung cancer). These potent activities highlight its efficacy at very low concentrations. The compound is cytotoxic to tumor cells due to its ability to induce DNA damage through topoisomerase I inhibition. Its activity is typically assessed in cell proliferation assays, with IC₅0 values determined after 48-72 hours of treatment. |
| ln Vivo |
In vivo activity of Topoisomerase I inhibitor 8 has been evaluated in animal models of cancer, though detailed data are limited. As a potent topoisomerase I inhibitor with picomolar to nanomolar in vitro activity, the compound is expected to exhibit antitumor efficacy in xenograft models. The compound's hexacyclic camptothecin-like structure suggests it may have improved stability and pharmacokinetic properties compared to camptothecin. However, specific in vivo efficacy data, including tumor growth inhibition rates and survival benefits, are not extensively reported in the available literature. The compound is primarily used for in vitro research applications.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Topoisomerase I inhibitor 8 involve measuring its ability to inhibit the catalytic activity of purified topoisomerase I. The assay typically uses recombinant human topoisomerase I and a supercoiled plasmid DNA substrate. The compound is incubated with the enzyme and DNA at 37degC for 30-60 minutes, and the reaction is terminated by adding SDS and proteinase K. The DNA products are resolved by agarose gel electrophoresis to visualize the conversion of supercoiled DNA to relaxed DNA. Inhibition is quantified by the concentration required to inhibit 50% of the enzyme activity (IC₅0). The compound's ability to stabilize the cleavage complex may also be assessed using specific cleavage assays.
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| Cell Assay |
Cellular assays for Topoisomerase I inhibitor 8 are conducted using cancer cell lines such as P388, HOC-21, and QG-56. Cells are cultured in appropriate media and treated with varying concentrations of the compound (typically 0.01-1000 ng/mL) for 48-72 hours. Cell viability is assessed using MTT, CCK-8, or sulforhodamine B (SRB) assays. IC₅0 values are calculated from dose-response curves. The compound's effects on cell cycle progression and apoptosis are evaluated using flow cytometry. DNA damage is assessed by measuring gamma-H2AX foci formation or comet assays. The compound's cytotoxicity is compared to that of camptothecin or other topoisomerase I inhibitors as positive controls.
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| Animal Protocol |
In vivo animal studies for Topoisomerase I inhibitor 8 are typically conducted in murine xenograft models using human tumor cell lines. Tumor-bearing mice are treated with the compound via intravenous, intraperitoneal, or oral administration at various doses. Tumor volume is measured regularly using calipers, and body weight is monitored to assess tolerability. At study termination, tumors are excised and analyzed for histopathology, apoptosis markers (TUNEL, caspase-3), and topoisomerase I activity. Pharmacokinetic studies may also be performed to determine plasma and tissue concentrations. However, specific in vivo study protocols and results are not extensively reported in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Topoisomerase I inhibitor 8 have not been extensively characterized in the literature. The compound has a molecular weight of 420.43 g/mol and a molecular formula of C24H21FNO4. It is a hexacyclic analogue of camptothecin, suggesting that it may share some pharmacokinetic properties with camptothecin derivatives, including limited aqueous solubility and potential instability of the lactone ring. The compound is typically stored at -20degC and is soluble in DMSO. Detailed PK parameters such as half-life, bioavailability, and volume of distribution are not reported in the available literature.
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| Toxicity/Toxicokinetics |
Toxicological data for Topoisomerase I inhibitor 8 are limited, as the compound is used primarily as a research tool rather than a therapeutic agent. The compound is not intended for human therapeutic use and is supplied for research purposes only. In cell-based assays, the compound is cytotoxic to tumor cells at sub-nanomolar to nanomolar concentrations, indicating potent activity. Its toxicity profile is expected to be similar to that of other topoisomerase I inhibitors, with potential off-target effects on rapidly dividing cells such as bone marrow and gastrointestinal epithelium. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Topoisomerase I inhibitor 8 is a potent inhibitor of topoisomerase I and a hexacyclic analogue of camptothecin. It exhibits potent anticancer activity against multiple cancer cell lines including P388, HOC-21, and QG-56, with IC₅0 values in the sub-nanomolar to low nanomolar range. The compound is cytotoxic to tumor cells and is used as a research tool for studying DNA replication, transcription, and cancer cell biology. It is not an FDA-approved drug and has no clinical indications. The compound is available in high purity (≥99.9%) and is typically stored at -20degC.
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| Molecular Formula |
C24H21FN2O4
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| Molecular Weight |
420.432949781418
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| Exact Mass |
420.148
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| CAS # |
210346-40-0
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| PubChem CID |
10025127
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| Appearance |
Light yellow to brown solid powder
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| LogP |
2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
31
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| Complexity |
915
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C5CCCC6=C5C(=CC(=C6C)F)N=C4C3=C2)O
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| InChi Key |
YLGVBUAQTQSHCD-DEOSSOPVSA-N
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| InChi Code |
InChI=1S/C24H21FN2O4/c1-3-24(30)16-7-19-21-14(9-27(19)22(28)15(16)10-31-23(24)29)13-6-4-5-12-11(2)17(25)8-18(26-21)20(12)13/h7-8,30H,3-6,9-10H2,1-2H3/t24-/m0/s1
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| Chemical Name |
(10S)-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaene-5,9-dione
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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 | 2.3785 mL | 11.8926 mL | 23.7852 mL | |
| 5 mM | 0.4757 mL | 2.3785 mL | 4.7570 mL | |
| 10 mM | 0.2379 mL | 1.1893 mL | 2.3785 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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