TAS0728

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.

Product information

CAS Number: 2088323-16-2

Molecular Weight: 504.58

Formula: C26H32N8O3

Synonym:

TPC 107

Chemical Name: (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-N-(4-(2-(dimethylamino)-2-oxoethyl)-2,3-dimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide

Smiles: CN(C)C(=O)CC1=CC=C(NC(=O)C2=NN([C@H]3CN(CCC3)C(=O)C=C)C3=NC=NC(N)=C32)C(C)=C1C

InChiKey: JCCIICHPRAAMGK-GOSISDBHSA-N

InChi: InChI=1S/C26H32N8O3/c1-6-20(35)33-11-7-8-18(13-33)34-25-22(24(27)28-14-29-25)23(31-34)26(37)30-19-10-9-17(15(2)16(19)3)12-21(36)32(4)5/h6,9-10,14,18H,1,7-8,11-13H2,2-5H3,(H,30,37)(H2,27,28,29)/t18-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO 100 mg/mL (198.18 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

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.

References:

1. Hiroki Irie, et al. Mol Cancer Ther. 2019 Apr;18(4):733-742.

Products are for research use only. Not for human use.