TAS0728

Catalog No.S8833 Batch:S883301

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Technical Data

Formula

C26H32N8O3
Molecular Weight 504.58 CAS No. 2088323-16-2
Solubility (25°C)* In vitro DMSO 100 mg/mL (198.18 mM)
Ethanol 5 mg/mL (9.9 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description TAS0728 (TPC 107) is a potent, selective, orally active, irreversible and covalent-binding inhibitor of HER2 (human epidermal growth factor receptor 2) with IC50 of 13 nM. TAS0728 inihibits BMX, HER4, BLK, EGFR, JAK3, SLK, LOK and human HER2 with IC50 of 4.9 nM, 8.5 nM, 31 nM, 65 nM, 33 nM, 25 nM, 86 nM and 36 nM, respectively. TAS0728 shows antitumor activity.
Targets
HER2 [1]
(Cell-free assay)
13 nM
In vitro

TAS0728 covalently binds to HER2 at C805 and selectively inhibits its kinase activity. Once TAS0728 binds to HER2 kinase, the inhibitory activity is not affected by a high ATP concentration. TAS0728 possesses high specificity for HER2 over wild-type EGFR. TAS0728 potently inhibits the phosphorylation of mutated HER2 and wild-type HER2. TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells.[1]
In vivo

TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis in tumor tissues of a xenograft model. TAS0728 induces tumor regression in mouse xenograft models bearing HER2 signal–dependent tumors and exhibits a survival benefit without any evident toxicity in a peritoneal dissemination mouse model bearing HER2-driven cancer cells.[1]

Protocol (from reference)

Kinase Assay:

[1]
  • HER2 kinase assay

    The inhibitory activity of HER2 kinase is measured using kinase profiling, performed by Carna Biosciences. The 50% inhibitory concentration (IC50 value) of TAS0728 is determined on the basis of the in vitro peptide substrate phosphorylation activity of HER2. Three independent experiments are conducted. The inhibitory activity of TAS0728 for 386 or 374 kinases is tested using Kinase Panel Assay at Reaction Biology Corporation. The assays are conducted in duplicate mode at concentrations of 0.1, 1, and 10 μmol/L TAS0728. Reactions are carried out in the presence of 10 μmol/L ATP.
Cell Assay:

[1]
  • Cell lines

    SK-BR-3 cells, A-431, AU565, BT-474, Calu-3, NCI-N87 cells, etc.

  • Concentrations

    40 nM, 10-1000 nM

  • Incubation Time

    3 h, 48 h, 72 h

  • Method

    Cells are seeded in 6-well plates and cultured overnight. Compounds are added to the culture medium at concentrations as indicated for 3 hours followed by harvesting for Western blot analysis. For studies using MCF10A cell line, cells are seeded in 12-well plates and incubated overnight. TAS0728 is added to the culture medium and incubated for 3 hours. The cells are harvested to perform Western blot analysis. In the pharmacodynamics time-course study, SK-BR-3 cells are seeded in 100-mm dishes and cultured overnight. TAS0728 is added and incubated for 3 or 48 hours. The cells are harvested to perform Western blot analysis.
Animal Study:

[1]
  • Animal Models

    6-week-old male nude mice (BALB/cAJcl-nu/nu)

  • Dosages

    7.5 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg

  • Administration

    Oral gavage

Selleck's TAS0728 has been cited by 1 publication

HER4 and EGFR activate cell signaling in NRG1 fusion-driven cancers: implications for HER2/HER3-specific vs. pan-HER targeting strategies [ J Thorac Oncol, 2023, S1556-0864(23)00802-X] PubMed: 37678511

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.