| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
Topoisomerase I 0.31 μM (IC50)
DNA topoisomerase I; functions as a potent inhibitor (IC50=0.31 microM), trapping topoisomerase I-DNA cleavage complexes and preventing DNA religation, leading to DNA damage and cell death. |
|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[2].
Unlabeled Dxd is a potent DNA topoisomerase I inhibitor with an IC50 of 0.31 microM. It induces DNA damage, G2/M cell cycle arrest, and apoptosis in HER2-expressing cancer cells when delivered as an ADC payload. The d5-labeled analog has identical biochemical activity. |
| ln Vivo |
Unlabeled Dxd, conjugated to trastuzumab via a cleavable linker (DS-8201a), exhibits potent antitumor activity in HER2-expressing xenograft models and in patients with HER2-positive metastatic breast cancer and other HER2-expressing solid tumors.
|
| Enzyme Assay |
Topoisomerase I inhibition is measured by a DNA relaxation assay: supercoiled pBR322 plasmid DNA is incubated with purified human topoisomerase I in the presence of Dxd (0.01-10 microM); relaxed DNA products are resolved by agarose gel electrophoresis and visualized by ethidium bromide staining.
|
| Cell Assay |
HER2-expressing cancer cells (e.g., NCI-N87, SK-BR-3) are treated with Dxd-d5 as internal standard; unlabeled Dxd (0.1-100 nM) or DS-8201a ADC is added; cell viability is measured by CellTiter-Glo; DNA damage is assessed by gammaH2AX Western blot; cell cycle and apoptosis are analyzed by flow cytometry.
|
| Animal Protocol |
Mice bearing HER2-expressing tumor xenografts are administered DS-8201a (1-10 mg/kg, IV, single dose) or unlabeled Dxd; plasma and tissue samples are collected; Dxd-d5 is added as internal standard; samples are extracted and analyzed by LC-MS/MS to quantify Dxd concentrations.
|
| ADME/Pharmacokinetics |
Identical to unlabeled Dxd; as a small molecule topoisomerase I inhibitor, Dxd has good tissue penetration and plasma half-life of approximately 6-10 hours in preclinical species. The d5 label does not alter ADME properties; it is used for accurate quantification of Dxd in ADC PK studies.
|
| Toxicity/Toxicokinetics |
No toxicity data for the d5 analog; Dxd as a topoisomerase I inhibitor has dose-limiting toxicities of myelosuppression (neutropenia, thrombocytopenia) and gastrointestinal effects (nausea, diarrhea). In ADC form (Enhertu), the safety profile is manageable with interstitial lung disease as a serious adverse event.
|
| References |
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| Additional Infomation |
Dxd (Exatecan derivative) is the active cytotoxic payload in the FDA-approved HER2-targeting ADC trastuzumab deruxtecan (Enhertu, DS-8201a). The d5-labeled analog is a research-grade analytical standard for LC-MS/MS quantification in ADC development.
|
| Molecular Formula |
C26H19D5FN3O6
|
|---|---|
| Molecular Weight |
498.51
|
| Related CAS # |
Exatecan mesylate;169869-90-3;Dxd;1599440-33-1;Exatecan mesylate dihydrate;197720-53-9
|
| Appearance |
White to off-white solid powder
|
| 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: 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)
|
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~200.60 mM)
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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 | 2.0060 mL | 10.0299 mL | 20.0598 mL | |
| 5 mM | 0.4012 mL | 2.0060 mL | 4.0120 mL | |
| 10 mM | 0.2006 mL | 1.0030 mL | 2.0060 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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