Home Protein Tyrosine Kinase HER2 inhibitor TAS0728

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TAS0728 HER2 inhibitor

Cat.No.S8833

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. This compound 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. It shows antitumor activity.
TAS0728 HER2 inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 504.58

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Quality Control

Chemical Information, Storage & Stability

Molecular Weight 504.58 Formula

C26H32N8O3

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 2088323-16-2 -- Storage of Stock Solutions

Synonyms TPC 107 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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (198.18 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 5 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC50/Ki
HER2 [1]
(Cell-free assay)
13 nM
In vitro

TAS0728 covalently binds to HER2 at C805 and selectively inhibits its kinase activity. Once this compound binds to HER2 kinase, the inhibitory activity is not affected by a high ATP concentration. It possesses high specificity for HER2 over wild-type EGFR. It potently inhibits the phosphorylation of mutated HER2 and wild-type HER2. It 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 this compound 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 of this chemical. Reactions are carried out in the presence of 10 μmol/L ATP.
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. This compound 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]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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