TAS0728

製品コードS8833 バッチS883302

印刷

化学情報

Chemical Structure Synonyms TPC 107 Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C26H32N8O3
分子量 504.58 CAS No. 2088323-16-2
Solubility (25°C)* 体外 DMSO 100 mg/mL (198.18 mM)
Water Insoluble
Ethanol 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 SK-BR-3 cells, A-431, AU565, BT-474, Calu-3, NCI-N87 cells, etc.
濃度 40 nM, 10-1000 nM
反応時間 3 h, 48 h, 72 h
実験の流れ

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.
動物実験 動物モデル 6-week-old male nude mice (BALB/cAJcl-nu/nu)
投薬量 7.5 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg
投与方法 Oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。