TAS0728
Based on 1 Customer Validation
TAS0728 is a potent, selective, orally active, irreversible and covalent-binding HER2 inhibitor, with an IC50 of 13 nM. TAS0728 also shows IC50s of 4.9, 8.5, 31, 65, 33, 25 and 86 nM for BMX、HER4、BLK、EGFR、JAK3、SLK and LOK respectively. Furthermore, TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors.
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- Pureté : 99.71%
- CAS No.: 2088323-16-2
- Formule: C26H32N8O3
- Masse moléculaire:504.58
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
HER4 8.5 nM (IC50) |
HER2 13 nM (IC50) |
EGFR 65 nM (IC50) |
BMX 4.9 nM (IC50) |
BLK 31 nM (IC50) |
JAK3 33 nM (IC50) |
SLK 25 nM (IC50) |
LOK 86 nM (IC50) |
In Vitro
TAS0728 is a covalent-binding inhibitor of HER2 kinase and exhibits high selectivity for HER2 kinase. It also shows inhibitory activity against BMX, HER4, BLK, EGFR, JAK3, SLK, and LOK[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HER2-amplified SK-BR-3/AU565/BT-474/NCI-N87/Calu-3 cells
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Concentration:
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Incubation Time:
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Result:The GI50 values of TAS0728 were 5.0/5.1/3.6/1.6/6.9 nM relatively for HER2-amplified SK-BR-3/AU565/BT-474/NCI-N87/Calu-3 cells.
Inhibited the in vitro proliferation of five HER2-amplified cell lines.
Showed potent inhibitory activities against cancer cell lines with HER2 amplification.
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Cell Line:SK-BR-3 cells
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Concentration:30-300 nM
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Incubation Time:3 and 48 hours
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Result:Showed sustained inhibition of HER2, HER3, AKT and ERK phosphorylation.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male nude mice
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Dosage:7.5, 15, 30 and 60 mg/kg
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Administration:Oral gavage; 7.5, 15, 30 and 60 mg/kg a day;14 days
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Result:Rapidly eliminated within 24 hours.
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Animal Model:Mice bearing NCI-N87 xenografts
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Dosage:60 mg/kg
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Administration:Oral gavage; 60 mg/kg a day; 14 days
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Result:Revealed sustained target inhibition of HER2, HER3, AKT and ERK.
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Animal Model:Mice with NCI-N87 HER2–amplified human gastric cancer
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Dosage:7.5, 15, 30 and 60 mg/kg
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Administration:Oral gavage; 7.5, 15, 30 and 60 mg/kg a day; 14 days
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Result:Well tolerated in all mice.
Significant tumor regression was observed in mice treated with 60 mg/kg/day.
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Animal Model:NCI-N87 peritoneal dissemination model
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Dosage:30 and 60 mg/kg
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Administration:Oral gavage; 30and 60 mg/kg a day; 120 days
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Result:No evident toxicity, including diarrhea and body weight loss in the long-term dosing of TAS0728.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2088323-16-2
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Appearance Solid
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Masse moléculaire 504.58
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Formule C26H32N8O3
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Color White to off-white
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SMILES
NC1=C2C(N([C@H]3CN(C(C=C)=O)CCC3)N=C2C(NC4=CC=C(CC(N(C)C)=O)C(C)=C4C)=O)=NC=N1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvant et solubilité
In Vitro:
DMSO : 125 mg/mL (247.73 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (4.12 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (4.12 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
Pureté et documentation
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Fiche technique (288 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.9818 mL | 9.9092 mL | 19.8185 mL | 49.5462 mL |
| 5 mM | 0.3964 mL | 1.9818 mL | 3.9637 mL | 9.9092 mL | |
| 10 mM | 0.1982 mL | 0.9909 mL | 1.9818 mL | 4.9546 mL | |
| 15 mM | 0.1321 mL | 0.6606 mL | 1.3212 mL | 3.3031 mL | |
| 20 mM | 0.0991 mL | 0.4955 mL | 0.9909 mL | 2.4773 mL | |
| 25 mM | 0.0793 mL | 0.3964 mL | 0.7927 mL | 1.9818 mL | |
| 30 mM | 0.0661 mL | 0.3303 mL | 0.6606 mL | 1.6515 mL | |
| 40 mM | 0.0495 mL | 0.2477 mL | 0.4955 mL | 1.2387 mL | |
| 50 mM | 0.0396 mL | 0.1982 mL | 0.3964 mL | 0.9909 mL | |
| 60 mM | 0.0330 mL | 0.1652 mL | 0.3303 mL | 0.8258 mL | |
| 80 mM | 0.0248 mL | 0.1239 mL | 0.2477 mL | 0.6193 mL | |
| 100 mM | 0.0198 mL | 0.0991 mL | 0.1982 mL | 0.4955 mL |
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