| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Traditional Cytotoxic Agents
Duocarmycin DM alkylates the N3 of adenine in the DNA minor groove. This alkylation disrupts the DNA structure, inhibits replication, and induces irreversible cell death, regardless of the cell cycle phase. |
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| ln Vitro |
In cell-free assays, the conjugated duocarmycin DM is inactive until the valine-citrulline (vc) linker is cleaved by lysosomal proteases (e.g., cathepsin B). The parent Duocarmycin DM is a highly potent DNA alkylating agent, with activity in the picomolar range against proliferating cancer cells.
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| ln Vivo |
The full ADC incorporating this linker-payload is used in vivo. In animal xenograft models, the duocarmycin DM ADC demonstrates potent and durable anti-tumor activity. The MA-PEG4 spacer allows for a high drug-to-antibody ratio (DAR) by preventing aggregation, thereby delivering a high dose of the potent DNA alkylator.
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| Enzyme Assay |
A general cell‑free protocol for Duocarmycin DM ADCs: The drug-linker conjugate is conjugated to a target antibody. The final ADC is incubated in a buffer containing cathepsin B to assess linker stability and payload release by LC-MS. In addition, the ADC's ability to alkylate DNA in a cell-free system can be measured using a DNA alkylation assay.
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| Cell Assay |
A general cellular protocol: Target-positive cancer cells are plated and treated with the Duocarmycin DM ADC for 72-96 hours. Cell viability is measured with a CellTiter-Glo assay. The DNA damage response can be assessed by Western blot for gamma-H2AX or by alkaline comet assays. Apoptosis is measured by Annexin V/PI staining.
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| Animal Protocol |
A general animal protocol: Mice bearing target-positive xenografts are dosed intravenously with the Duocarmycin DM ADC at 1, 3, or 10 mg/kg. Tumor volume is measured bi-weekly. At the end of the study, tumors are excised for analysis of DNA damage (gamma-H2AX), cell death (TUNEL), and proliferation (Ki-67).
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| ADME/Pharmacokinetics |
The PK of the Duocarmycin DM ADC, not the linker, is assessed. Following IV administration in rats, plasma is collected over 28 days and analyzed by ELISA for the conjugated antibody and LC-MS/MS for the released payload to derive parameters like clearance and half-life.
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| Toxicity/Toxicokinetics |
General toxicity protocol for Duocarmycin DM ADCs: A 14-day repeat-dose IV toxicity study in rats (doses of 5, 15, 45 mg/kg) is performed. Parameters include clinical signs, body weight, hematology, serum chemistry, and histopathology of the bone marrow, liver, and gastrointestinal tract, as these are the major sites of duocarmycin's on-target toxicity.
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| References | |
| Additional Infomation |
Duocarmycin DM is a highly potent DNA minor groove alkylator. Its potency necessitates careful linker design to avoid premature release and systemic toxicity. The TFA (trifluoroacetate) salt form enhances solubility. The drug-linker conjugate has a molecular formula of C70H90ClF3N12O19 and a molecular weight of 1495.98 g/mol.
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| Molecular Formula |
C70H90CLF3N12O19
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|---|---|
| Molecular Weight |
1495.98
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| Appearance |
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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | 0.6685 mL | 3.3423 mL | 6.6846 mL | |
| 5 mM | 0.1337 mL | 0.6685 mL | 1.3369 mL | |
| 10 mM | 0.0668 mL | 0.3342 mL | 0.6685 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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