| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Spliceosome. Thailanstatin A and its analogs inhibit the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs) that is essential for pre-mRNA splicing, thereby disrupting gene expression and inducing cancer cell death.
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|---|---|
| ln Vitro |
In cell‑free activity assays, Thailanstatin A cyclohexane diamine formic potently inhibits the proliferation of several cancer cell lines. It has IC50 values of 0.33 microM in N87 cells, 0.34 microM in BT474 cells, 0.88 microM in MDA-MB-361-DYT2 cells, and 0.27 microM in MDA-MB-468 cells, demonstrating its potent broad-spectrum anti-proliferative activity.
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| ln Vivo |
This compound is not typically used alone in vivo but rather conjugated to a tumor-targeting antibody. However, its potent in vitro activity suggests that when delivered as an ADC, it would effectively inhibit tumor growth in xenograft models by blocking the spliceosome and inducing apoptosis in targeted cancer cells.
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| Enzyme Assay |
A general cell‑free protocol for assessing cytotoxicity: N87, BT474, or other cancer cells are seeded in 96-well plates and treated with serial dilutions of Thailanstatin A cyclohexane diamine formic for 72 hours. Cell viability is measured using a CellTiter-Glo or MTT assay, and the half-maximal inhibitory concentration (IC50) is calculated from the resulting dose-response curve.
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| Cell Assay |
A general cellular protocol for testing the ADC: Target-positive cancer cells are plated and treated with the Thailanstatin A-based ADC. After a 72-hour incubation, cell viability is measured with a CellTiter-Glo assay, and the IC50 is compared to that of the free payload to determine the activity of the conjugate.
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| Animal Protocol |
A general animal protocol for the Thailanstatin A ADC: Mice bearing xenografts of target-positive cancer cells (e.g., MDA-MB-468 breast cancer) are treated intravenously with the ADC at doses of 1, 3, or 10 mg/kg. Tumor growth inhibition (TGI) is monitored and compared to vehicle and non-binding ADC controls to assess target-specific efficacy.
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| ADME/Pharmacokinetics |
The PK of the Thailanstatin A ADC, not the free payload, is measured. Following IV administration to rodents or cynomolgus monkeys, plasma samples are analyzed by ELISA for total antibody and conjugated antibody concentrations. The PK profile is characterized by a slow clearance and a long terminal half-life.
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| Toxicity/Toxicokinetics |
General toxicity for the Thailanstatin A ADC is assessed in a 28-day repeat-dose study in rats. The ADC is administered intravenously at doses of 10, 30, and 100 mg/kg once weekly. Parameters evaluated include clinical signs, body weight, hematology, serum chemistry, and histopathology of the liver, kidneys, and gastrointestinal tract.
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| References | |
| Additional Infomation |
Thailanstatin A is a natural product originally isolated from the bacterium Thailanstatin, and it is a potent inhibitor of the spliceosome. The cyclohexane diamine formic salt is used to improve its water solubility and facilitate conjugation to antibodies for ADC development, a field of targeted cancer therapy.
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| Molecular Formula |
C35H55N3O10
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|---|---|
| Molecular Weight |
677.83
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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 | 1.4753 mL | 7.3765 mL | 14.7530 mL | |
| 5 mM | 0.2951 mL | 1.4753 mL | 2.9506 mL | |
| 10 mM | 0.1475 mL | 0.7376 mL | 1.4753 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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