| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Topoisomerase I (Top1). This enzyme is responsible for relieving torsional stress in DNA during replication and transcription by creating transient single-strand breaks. Camptothecin derivatives, including this compound, bind to and stabilize the Top1-DNA cleavage complex, preventing DNA religation and leading to the accumulation of DNA double-strand breaks during replication, which ultimately triggers apoptosis. As an ADC payload, it is internalized by cancer cells and released to exert its topoisomerase I inhibitory effect.
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| ln Vitro |
In vitro, this compound is a potent topoisomerase I inhibitor, a characteristic of camptothecin derivatives. It has been shown to induce cytotoxicity in various cancer cell lines, including those that are resistant to conventional therapies. As an ADC payload, it is designed to be highly potent (low picomolar to low nanomolar IC50s) to ensure that once delivered to the cancer cell by the antibody, it can effectively kill it. Its mechanism involves inhibition of DNA topoisomerase I, an enzyme crucial for DNA replication and transcription.
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| ln Vivo |
In vivo efficacy is achieved via ADC delivery. The free payload itself is typically too toxic to administer systemically; instead, it is conjugated to a tumor-targeting antibody via a linker (e.g., MC-AAA-NHCH2OCH2COO) to form an ADC. Upon binding to the target antigen on the cancer cell surface, the ADC is internalized, and the linker is cleaved (e.g., by lysosomal enzymes) to release the active payload. This targets the cytotoxic effect to the tumor while minimizing systemic exposure, leading to tumor regression in xenograft models.
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| Enzyme Assay |
For non-cell assays, a topoisomerase I inhibition assay is performed. This involves incubating purified human topoisomerase I with a supercoiled DNA plasmid (e.g., pHOT1) and varying concentrations of the test compound. The reaction mixture is incubated at 37degC for 30 minutes. The DNA products are then separated by agarose gel electrophoresis. Cleavage of the supercoiled DNA (Form I) to the nicked circular (Form II) and linear (Form III) forms indicates topoisomerase I activity. The test compound stabilizes the cleavable complex, leading to an accumulation of cleaved DNA fragments, which can be quantified by gel electrophoresis or using a radiolabeled DNA substrate.
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| Cell Assay |
For cellular activity, the ADC is tested in vitro using target antigen-positive cancer cell lines (e.g., HER2-positive SK-BR-3 cells for an anti-HER2 ADC). Cells are seeded in 96-well plates and treated with serial dilutions of the ADC (0.001-100 nM). After 96-120 hours, cell viability is measured using the CellTiter-Glo luminescent assay. The free payload is used as a comparator. Cytotoxicity is typically observed in the low nM to pM range. The TFA salt form is often used to improve solubility.
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| Animal Protocol |
For the ADC, in vivo efficacy is evaluated in immunodeficient mice bearing established human tumor xenografts. When tumors reach ~150-200 mm3, mice are randomized (n=8-10 per group) and treated intravenously (IV) with a single dose (e.g., 1-10 mg/kg) or multiple doses (e.g., QW x 3) of the ADC. Tumor volumes are measured by calipers twice weekly, and body weight is monitored. The ADC should demonstrate significant tumor growth inhibition or regression compared to the vehicle control. At the end of the study, tumors can be collected for PK/PD analysis.
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| ADME/Pharmacokinetics |
The payload is not typically dosed as a free drug in vivo. For the ADC, the payload is released only after antibody binding and internalization. The linker and conjugation site influence the stability and PK of the ADC in circulation. The free drug 7-Aminomethyl-10-methyl-11-fluoro camptothecin has a molecular formula of C22H20FN3O4 and a molecular weight of 409.41. It is soluble in DMSO. For formulation, a vehicle of 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline is often used for preclinical studies. Storage conditions: -20degC, sealed, away from moisture and light; in solvent: -80degC for 6 months or -20degC for 1 month.
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| Toxicity/Toxicokinetics |
The free camptothecin payload is highly toxic. ADC payloads are designed to be potent cytotoxins. The primary toxicity of camptothecin derivatives is bone marrow suppression (neutropenia, thrombocytopenia) and gastrointestinal toxicity (diarrhea, nausea, vomiting). The TFA salt is non-toxic at the concentrations used. The compound is for research use only and not for human therapeutic use.
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| References | |
| Additional Infomation |
7-Aminomethyl-10-methyl-11-fluoro camptothecin is a research-grade chemical that functions as a potent cytotoxic payload for antibody-drug conjugates (ADCs). It is a derivative of the natural product camptothecin, and its mechanism of action is through the inhibition of DNA topoisomerase I. It is classified as an alkaloid and an anticancer drug. It is used primarily in oncology research to develop ADCs for the treatment of solid tumors and hematologic malignancies. It is not FDA-approved as a standalone drug and is for research use only (RUO).
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| Molecular Formula |
C24H21F4N3O6
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|---|---|
| Molecular Weight |
523.43
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| Related CAS # |
7-Aminomethyl-10-methyl-11-fluoro camptothecin;2378616-23-8
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| Appearance |
Light yellow to yellow solid powder
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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) |
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 | 1.9105 mL | 9.5524 mL | 19.1048 mL | |
| 5 mM | 0.3821 mL | 1.9105 mL | 3.8210 mL | |
| 10 mM | 0.1910 mL | 0.9552 mL | 1.9105 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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