Home Protein Tyrosine Kinase HER2 inhibitor TAS0728 For research use only.

TAS0728

Synonyms: TPC 107

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.

TAS0728 Chemical Structure

TAS0728 Chemical Structure

CAS No. 2088323-16-2

Purity & Quality Control

TAS0728 Related Products

Signaling Pathway

HER2 Signaling Pathways

HER2 Signaling Pathway

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
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]
Kinase Assay 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 Research 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.
In Vivo
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]
Animal Research 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03410927 Terminated
Advanced Solid Tumors With HER2 Abnormalities|Advanced Solid Tumors With HER3 Abnormalities
Taiho Oncology Inc.
 April 6 2018 Phase 1

Chemical Information & Solubility

Molecular Weight 504.58 Formula

C26H32N8O3
CAS No. 2088323-16-2 SDF --
Smiles CC1=C(C=CC(=C1C)NC(=O)C2=NN(C3=NC=NC(=C23)N)C4CCCN(C4)C(=O)C=C)CC(=O)N(C)C
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (198.18 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 5 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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