| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
The target of the unlabeled version, trabectedin, is the DNA minor groove. Trabectedin binds to the minor groove of DNA, forming adducts that interfere with DNA-binding proteins and transcription factors. This leads to the blockage of stress-induced protein transcription and the activation of DNA damage response pathways. Ultimately, this causes DNA backbone cleavage and induces cell cycle arrest and apoptosis in cancer cells. Trabectedin-d3 is intended for use as an analytical standard to study the interaction of the parent drug with this target, allowing for precise quantification in various research contexts.
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| ln Vitro |
In vitro activity is attributed to the parent compound, trabectedin. It demonstrates potent antitumor activity in various cancer cell lines. Trabectedin has been shown to bind to the minor groove of DNA, which blocks the transcription of stress-induced proteins and induces DNA backbone cleavage, leading to cancer cell apoptosis. It also increases reactive oxygen species (ROS) production in MCF-7 and MDA-MB-453 breast cancer cells. These in vitro activities are the benchmark for which the labeled version is used as an analytical tool for quantification and tracking in metabolism studies.
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| ln Vivo |
The in vivo activity of trabectedin has been extensively studied, and it is an approved drug for the treatment of soft tissue sarcoma and ovarian cancer. In animal models, trabectedin has been shown to significantly inhibit tumor growth and prolong survival. As a deuterated internal standard, Trabectedin-d3 is not used for its own activity but to accurately measure the in vivo pharmacokinetics and tissue distribution of the parent drug following its administration. This is critical for understanding the drug's absorption, metabolism, and excretion (ADME) profile.
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| Enzyme Assay |
For binding studies, the interaction of the unlabeled version, trabectedin, with its DNA target is typically studied by methods such as surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or gel mobility shift assays. A typical assay involves incubating a short oligonucleotide fragment of DNA with increasing concentrations of the compound. The binding is measured by the change in a physical property (e.g., mass, heat, or mobility). The deuterated version would be used as a control or internal standard in these assays to measure the unbound concentration of the unlabeled drug.
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| Cell Assay |
To construct a PROTAC molecule, the terminal primary amine is conjugated to a target protein ligand containing a carboxylic acid via standard amide coupling chemistry using HATU or EDCI/HOBt. The reaction is typically performed in anhydrous DMF or DMSO with DIPEA as base at room temperature for 2-12 hours. The resulting PROTAC is purified by preparative HPLC and characterized by LC-MS. For cellular activity validation, cells are treated with the PROTAC (0.001-10 uM, 4-24 h), then lysed and analyzed by western blotting to assess target protein degradation. Control treatments include the unconjugated target ligand alone and the CRBN ligand alone.
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| Animal Protocol |
Trabectedin-d3 is used as an internal standard in in vivo animal studies for LC-MS/MS analysis. A typical animal study involves administering unlabeled trabectedin to rodents (e.g., mice or rats) via intravenous (IV) injection at a therapeutic dose (e.g., 0.1-1 mg/kg). Blood samples are collected at various time points (e.g., 0, 15, 30, 60, 120, 240, and 480 minutes). A known amount of Trabectedin-d3 is then added to the plasma samples as an internal standard. The samples are processed (protein precipitation, extraction) and analyzed by LC-MS/MS to generate a concentration-time curve. This provides the pharmacokinetic parameters for the unlabeled drug, which are essential for understanding its in vivo behavior.
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| ADME/Pharmacokinetics |
Trabectedin-d3 is not a therapeutic agent; it is an analytical standard. Therefore, its pharmacokinetic properties (absorption, distribution, metabolism, excretion) are not directly studied. Instead, it is used as a tool to study the pharmacokinetics of the unlabeled drug, trabectedin. The stability of the label allows it to be used as an accurate tracer. The compound is stored as a powder at -20degC to maintain its stability, and as an internal standard, it is critical that it is chemically stable and does not degrade during the sample preparation and analysis process. It is typically stored under nitrogen, protected from moisture and light [29L10-L12].
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| Toxicity/Toxicokinetics |
Specific toxicity data for Trabectedin-d3 is not available, as it is not administered as a therapy. The toxicity of the parent compound, trabectedin, is well-documented and includes myelosuppression (low blood counts), hepatotoxicity (liver damage), and cardiotoxicity. Trabectedin-d3 is used in such small quantities as an internal standard (typically at ng/mL concentrations) that it poses negligible risk to the researcher. However, as with all laboratory chemicals, standard safety precautions should be followed. It is strictly for research use only, not for human consumption.
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| References |
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| Additional Infomation |
Trabectedin-d3 is a stable isotope-labeled research standard for the approved anticancer drug, trabectedin. Its primary function is to serve as an internal standard for the accurate quantification of the anti-cancer drug using mass spectrometry-based methods (LC-MS). The compound is a tetrahydroisoquinoline alkaloid with potent anti-tumor activity, and its mechanism of action involves binding to the minor groove of DNA, blocking transcription and inducing apoptosis. It is strictly a research tool and is not intended for clinical or therapeutic use. The compound is typically stored as a solid under inert conditions at -20degC to ensure its stability [29L9-L12].
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| Molecular Formula |
C39H40D3N3O11S
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| Related CAS # |
Trabectedin;114899-77-3
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| Appearance |
Typically exists as solid at room temperature
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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.) |
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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