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TAS0728 HER2 inhibitor

Name: TAS0728
Brand: Selleck Chemicals
SKU: S8833
Availability: InStock
Rating: 5 (1 reviews)

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.

Chemical Structure

Molecular Weight: 504.58

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Quality Control

Batch: Purity: 99.31%

99.31

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 c-Kit
Other HER2 Inhibitors	CP-724714 Sapitinib (AZD8931) Mubritinib (TAK 165) AC480 (BMS-599626) Tyrphostin AG 879 HER2-Inhibitor-1 Zongertinib (BI 1810631)

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
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.91mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.830mg/ml (1.64mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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	1 year-80°Cin solvent 1 month-20°Cin solvent
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

Mechanism of Action

Targets/IC₅₀/Ki	HER2 (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.
Kinase Assay	HER2 kinase assay
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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/30787176/

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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