| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
ADC Control Human IgG1-Deruxtecan (DAR 8) does not have a specific antigen target because it is an isotype control antibody that does not bind to any human antigen. Its effector function as an ADC is mediated by the conjugated Deruxtecan payload, which is a potent inhibitor of DNA topoisomerase I. After binding to an antigen (via non-specific interactions), the ADC is internalized into cells, and the Deruxtecan payload is released. Deruxtecan inhibits topoisomerase I, leading to DNA damage and cell death. However, as an isotype control, it is used to distinguish target-specific ADC effects from non-specific effects of the antibody backbone or payload.
|
|---|---|
| ln Vitro |
In vitro, ADC Control Human IgG1-Deruxtecan (DAR 8) exhibits cytotoxic activity against cancer cells due to the release of the Deruxtecan payload, which is a potent topoisomerase I inhibitor. However, because the antibody does not bind specifically to cancer cell surface antigens, the cytotoxic effect is mediated by non-specific uptake (e.g., pinocytosis or Fc receptor-mediated internalization) and is typically less potent and less selective than that of a target-specific ADC. In experiments, the ADC control is used as a negative control to assess the specificity of the target ADC. In the absence of specific antigen binding, the control ADC provides a baseline level of cytotoxicity.
|
| ln Vivo |
Specific in vivo activity data for ADC Control Human IgG1-Deruxtecan (DAR 8) is not detailed in the search results. As an isotype control ADC, it is typically administered to xenograft-bearing mice as a control group in ADC efficacy studies. In such studies, the control ADC may exhibit low levels of anti-tumor activity due to non-specific uptake and payload release, but its effect is generally less than that of a target-specific ADC. The control ADC is used to demonstrate that the observed anti-tumor activity of a test ADC is due to specific antigen targeting rather than non-specific effects of the antibody or payload.
|
| Enzyme Assay |
The ADC control does not have a conventional enzyme/receptor binding assay because it is an antibody that does not bind specifically to any protein target. However, the potency of the payload can be assessed in a topoisomerase I inhibition assay. Procedure: Recombinant human topoisomerase I (1 unit) is incubated with varying amounts of Deruxtecan (the payload) or ADC Control at 37degC for 10 minutes in reaction buffer (10 mM Tris-HCl, pH 7.5, 50 mM KCl, 5 mM MgCl2, 0.1 mM EDTA, 15 microg/mL BSA). Supercoiled pBR322 plasmid DNA (500 ng) is added, and the reaction is allowed to proceed for 30 minutes. The reaction is stopped by adding SDS (0.5% final concentration). Relaxed DNA products are separated by agarose gel electrophoresis (1% agarose, 0.5 microg/mL ethidium bromide) and visualized under UV light. The IC50 is determined as the concentration that inhibits 50% of DNA relaxation compared to control. Alternatively, Deruxtecan and ADC Control can be tested for their ability to inhibit cell proliferation using various cancer cell lines, as described in the cell experiment section.
|
| Cell Assay |
The cytotoxic activity can be assessed in cancer cell lines to evaluate the potency of the Deruxtecan payload and to serve as a control for target-specific ADCs. Procedure: Various cancer cell lines (e.g., SK-BR-3, NCI-N87, or other HER2-expressing cells for target-specific ADC controls, or any cell line for non-specific effects) are seeded in 96-well plates at 5,000-10,000 cells per well and allowed to attach overnight. Cells are treated with serial dilutions of ADC Control Human IgG1-Deruxtecan (DAR 8) (e.g., 0.001, 0.01, 0.1, 1, 10, 100 nM) and incubated for 72-96 hours at 37degC. Cell viability is measured using CellTiter-Glo luminescent assay or MTS assay. IC50 values are calculated from dose-response curves. The cytotoxic activity of the ADC control is compared to that of the target-specific ADC (e.g., trastuzumab-deruxtecan for HER2-positive cancer cells) to assess specificity. The ADC control should show significantly weaker or equivalent activity depending on the level of non-specific uptake by the cell line.
|
| Animal Protocol |
The in vivo control experiment can be performed in a xenograft mouse model of cancer. Procedure: 6-8 week old female athymic nude mice are inoculated subcutaneously with 5×10^6 cancer cells (e.g., HER2-positive SK-BR-3 or NCI-N87 cells) in 50% Matrigel. When tumors reach an average volume of 150-200 mm3, mice are randomized into treatment groups (n=8-10 per group). Groups include: vehicle control (PBS), target-specific ADC (e.g., anti-HER2-Deruxtecan at 10 mg/kg), and ADC Control Human IgG1-Deruxtecan (DAR 8) at matching doses (e.g., 10 mg/kg). ADCs are administered intravenously (tail vein injection) on days 0, 7, and 14 (q7d × 3). Tumor volumes are measured with digital calipers every 3-4 days. Body weights are recorded to monitor toxicity. At study endpoint (typically day 21-28), tumors are harvested and weighed. Tumor growth inhibition (TGI) is calculated as the percentage reduction in tumor volume compared to the vehicle control group. A significantly greater TGI in the target-specific ADC group compared to the control ADC group confirms antigen-specific anti-tumor activity.
|
| ADME/Pharmacokinetics |
As a full-length monoclonal antibody (human IgG1, 150 kDa) conjugated to eight small molecule Deruxtecan payloads, ADC Control Human IgG1-Deruxtecan (DAR 8) has a total molecular weight of approximately 160-165 kDa. Pharmacokinetic properties are typical of monoclonal antibodies: slow clearance (half-life of 5-10 days in mice, 15-20 days in humans), low volume of distribution (primarily confined to the intravascular and interstitial spaces), and low oral bioavailability (requiring intravenous administration). The Deruxtecan payload is released after internalization of the ADC into cells. The antibody portion is metabolized into peptides and amino acids by proteases. The presence of the PEG-based linker may slightly alter the PK compared to unconjugated antibodies. For in vivo studies, the ADC is typically administered intravenously at doses of 1-30 mg/kg.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for ADC Control Human IgG1-Deruxtecan (DAR 8) is not provided in the search results. As an ADC containing the potent topoisomerase I inhibitor Deruxtecan, its toxicity profile may include the class-related toxicities of topoisomerase I inhibitors (e.g., gastrointestinal toxicities, bone marrow suppression). However, as an isotype control with no specific antigen binding, its toxicity may be lower than that of a target-specific ADC because it does not accumulate specifically in tumor tissues. In vivo toxicity studies in mice would be required to determine the maximum tolerated dose (MTD) and dose-limiting toxicities.
|
| References | |
| Additional Infomation |
ADC Control Human IgG1-Deruxtecan (DAR 8) is an isotype control ADC used in preclinical research to validate the specificity and efficacy of target-specific ADCs that utilize the Deruxtecan payload and the human IgG1 framework. Deruxtecan is a potent topoisomerase I inhibitor that is the cytotoxic payload of the clinically approved ADC trastuzumab deruxtecan (Enhertu®), which targets HER2-positive breast and gastric cancers. This ADC control has a drug-to-antibody ratio (DAR) of 8, which is the same DAR as clinically used Deruxtecan-based ADCs, ensuring that any differences in activity between the control and a test ADC are due to target specificity rather than differences in payload loading. The antibody portion is human IgG1 kappa with no known binding to human antigens, making it an appropriate negative control to account for non-specific ADC effects. The product is for research use only and is not an approved drug for human use. It is typically stored at -20degC or -80degC to maintain stability.
|
| Appearance |
Colorless to light yellow liquid
|
|---|---|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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.) |
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
