TAS0728
TAS0728 Basic information
- Product Name:
- TAS0728
- Synonyms:
-
- TAS0728
- TAS0728;TAS-0728;TAS 0728
- 1H-Pyrazolo[3,4-d]pyrimidine-3-carboxamide, 4-amino-N-[4-[2-(dimethylamino)-2-oxoethyl]-2,3-dimethylphenyl]-1-[(3R)-1-(1-oxo-2-propen-1-yl)-3-piperidinyl]-
- TAS 0728,Inhibitor,EGFR,ErbB-1,inhibit,TAS0728,HER1,TAS-0728,Epidermal growth factor receptor
- (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
- TAS0728, 10 mM in DMSO
- AS0728
- TPC-107
- CAS:
- 2088323-16-2
- MF:
- C26H32N8O3
- MW:
- 504.58
- Mol File:
- 2088323-16-2.mol
TAS0728 Chemical Properties
- Boiling point:
- 721.8±60.0 °C(Predicted)
- Density
- 1.35±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO : 125 mg/mL (247.73 mM; Need ultrasonic)
- form
- A crystalline solid
- pka
- 10.24±0.70(Predicted)
- color
- White to off-white
TAS0728 Usage And Synthesis
Uses
TAS0728 is a potent, selective, orally active, irreversible and covalent-binding HER2 inhibitor, with an IC50 of 13 nM. TAS0728 also shows IC50s of 4.9, 8.5, 31, 65, 33, 25 and 86 nM for BMX、HER4、BLK、EGFR、JAK3、SLK and LOK respectively. Furthermore, TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors[1].
in vivo
TAS0728 reveals the sustained and targeted inhibition of phosphorylation of HER2, HER3, AKT and ERK. TAS0728 also shows the ability of tumor regression and low toxicity[1].
| Animal Model: | Male nude mice |
| Dosage: | 7.5, 15, 30 and 60 mg/kg |
| Administration: | Oral gavage; 7.5, 15, 30 and 60 mg/kg a day;14 days |
| Result: | Rapidly eliminated within 24 hours. |
| Animal Model: | Mice bearing NCI-N87 xenografts |
| Dosage: | 60 mg/kg |
| Administration: | Oral gavage; 60 mg/kg a day; 14 days |
| Result: | Revealed sustained target inhibition of HER2, HER3, AKT and ERK. |
| Animal Model: | Mice with NCI-N87 HER2–amplified human gastric cancer |
| Dosage: | 7.5, 15, 30 and 60 mg/kg |
| Administration: | Oral gavage; 7.5, 15, 30 and 60 mg/kg a day; 14 days |
| Result: | Well tolerated in all mice. Significant tumor regression was observed in mice treated with 60 mg/kg/day. |
| Animal Model: | NCI-N87 peritoneal dissemination model |
| Dosage: | 30 and 60 mg/kg |
| Administration: | Oral gavage; 30and 60 mg/kg a day; 120 days |
| Result: | No evident toxicity, including diarrhea and body weight loss in the long-term dosing of TAS0728. |
IC 50
HER4: 8.5 nM (IC50); HER2: 13 nM (IC50); EGFR: 65 nM (IC50); BMX: 4.9 nM (IC50); BLK: 31 nM (IC50); JAK3: 33 nM (IC50); SLK: 25 nM (IC50); LOK: 86 nM (IC50)
References
[1] Irie H, et al. TAS0728, A Covalent-binding, HER2-selective Kinase Inhibitor Shows Potent Antitumor Activity in Preclinical Models. Molecular cancer therapeutics. 2019;18(4):733-42. Epub 2019/02/23. DOI:10.1158/1535-7163.MCT-18-1085
TAS0728Supplier
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