| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Topoisomerase I. Exatecan, the parent drug, stabilizes the DNA‑topoisomerase I complex, preventing DNA re‑ligation and leading to DNA double‑strand breaks, replication fork collapse, and cell death. (4‑NH2)‑Exatecan‑d5 retains this inhibitory activity.
|
|---|---|
| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, primarily as quantitative tracers during drug development. Studies involving the use of deuterium-labeled drugs in humans have shown that these compounds may have certain advantages over their non-deuterated counterparts. Deuterated drugs have attracted attention due to their potential to affect the pharmacokinetic and metabolic characteristics of drugs. Deuttetrabenazine is the first deuterated drug approved by the United States Food and Drug Administration. Deuttetrabenazine is indicated for the treatment of chorea associated with Huntington's disease and tardive dyskinesia. Ongoing clinical trials indicate that many other deuterated compounds are being evaluated for use as therapeutics in humans, rather than simply as research tools. [1] (4-NH2)-Exatecan contains a linker for attaching a ligand unit, wherein the linker is cleavably attached to an amino residue and is characterized by the addition of an amino (NH2) functional group at the 4 position of the parent molecule [2].
In cell‑free assays, the Exatecan derivative inhibits the activity of topoisomerase I. The NH2 group and the deuterium atoms do not affect the intrinsic topoisomerase I inhibition potency. It can be used in antibody‑drug conjugate (ADC) development as a payload. The specific IC50 is not provided. |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
In vivo, the non‑deuterated (4‑NH2)‑Exatecan is used as the payload for ADCs. When conjugated to a tumor‑targeting antibody, the ADC accumulates in tumors, is internalized, and releases the active Exatecan, leading to tumor regression in xenograft models. The deuterated version is an analytical standard, not used for in vivo efficacy studies. |
| Enzyme Assay |
A general cell‑free protocol for (4‑NH2)‑Exatecan‑d5 is not applicable, as it is an internal standard. For its non‑deuterated counterpart, a topoisomerase I inhibition assay would be used: purified topoisomerase I is incubated with a supercoiled plasmid DNA and varying concentrations of the Exatecan derivative. The reaction is stopped, and the DNA products are separated by agarose gel electrophoresis. The conversion of supercoiled DNA to nicked and linear forms is quantified to determine the IC50.
|
| Cell Assay |
General cellular protocol for an ADC containing (4‑NH2)‑Exatecan: Target‑positive cancer cells are seeded in 96‑well plates. The ADC is added at serial dilutions. After 72‑96 hours, cell viability is measured by the CellTiter‑Glo assay. Cytotoxicity is compared to a non‑targeting control ADC to confirm specificity. The IC50 is calculated.
|
| Animal Protocol |
A general animal protocol for an ADC containing (4‑NH2)‑Exatecan: Nude mice bearing subcutaneous xenografts of target‑positive tumors are treated intravenously with the ADC at doses of 1, 3, and 10 mg/kg once weekly for three weeks. Tumor volume is measured twice weekly. At the end of the study, tumors are collected for IHC (Ki‑67, gammaH2AX) and TUNEL staining.
|
| ADME/Pharmacokinetics |
General PK protocol for (4‑NH2)‑Exatecan‑d5 as an internal standard: The compound is used to accurately quantify the ADC payload in plasma and tissues. A typical protocol involves spiking a known amount of the deuterated standard into a biological sample. After sample preparation (protein precipitation, solid‑phase extraction), the sample is analyzed by LC‑MS/MS. The peak area ratio of the analyte to the internal standard is used to calculate the analyte concentration.
|
| Toxicity/Toxicokinetics |
General toxicity protocol for an ADC containing (4‑NH2)‑Exatecan: A 28‑day repeat‑dose intravenous toxicity study would be performed in cynomolgus monkeys. The ADC would be administered at doses of 10, 30, and 100 mg/kg once weekly. Standard parameters include clinical signs, body weight, hematology (with special attention to platelet and neutrophil counts), serum chemistry, and histopathology. GI toxicity and myelosuppression are common for topoisomerase I inhibitor ADCs.
|
| References | |
| Additional Infomation |
(4‑NH2)‑Exatecan‑d5 is a stable isotope‑labeled derivative of Exatecan. It is a topoisomerase I inhibitor and is used as a payload for antibody‑drug conjugates (ADCs). The deuterium labeling (five deuterium atoms) provides a mass shift, enabling its use as an internal standard for LC‑MS bioanalysis. The compound contains a primary amine functional group that can be used to attach various linkers for ADC synthesis. It is a research chemical for oncology drug development.
|
| Molecular Formula |
C23H16D5N3O4
|
|---|---|
| Molecular Weight |
408.46
|
| Appearance |
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 : 33.33 mg/mL (81.60 mM; with sonication)
|
|---|---|
| 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 | 2.4482 mL | 12.2411 mL | 24.4822 mL | |
| 5 mM | 0.4896 mL | 2.4482 mL | 4.8964 mL | |
| 10 mM | 0.2448 mL | 1.2241 mL | 2.4482 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
