TAS0728 是一种有效的、选择性的、口服活性的、不可逆的共价结合HER2抑制剂，其IC50为13 nM。TAS0728 对于BMX、HER4、BLK、EGFR、JAK3、SLK和LOK也存在抑制效果，其IC50值分别为 4.9、8.5、31、65、33、25 和 86 nM。此外，TAS0728 对HER2、HER3和下游效应蛋白的磷酸化还表现出强大而持久的抑制作用。
| 生物活性 | TAS0728 is a potent, selective, orally active, irreversible and covalent-bindingHER2inhibitor, with anIC50of 13 nM. TAS0728 also showsIC50s of 4.9, 8.5, 31, 65, 33, 25 and 86 nM forBMX、HER4、BLK、EGFR、JAK3、SLKandLOKrespectively. Furthermore, TAS0728 exhibits robust and sustained inhibition of the phosphorylation ofHER2HER3, and downstream effectors[1]. |
| IC50& Target[1] | 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) |
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体外研究
(In Vitro) | TAS0728 is a covalent-binding inhibitor of HER2 kinase and exhibits high selectivity for HER2 kinase. It also shows inhibitory activity against BMX, HER4, BLK, EGFR, JAK3, SLK, and LOK[1].
Cell Cytotoxicity Assay[1] | Cell Line: | HER2-amplified SK-BR-3/AU565/BT-474/NCI-N87/Calu-3 cells | | Concentration: | | | Incubation Time: | | | Result: | The GI50values of TAS0728 were 5.0/5.1/3.6/1.6/6.9 nM relatively for HER2-amplified SK-BR-3/AU565/BT-474/NCI-N87/Calu-3 cells.
Inhibited the in vitro proliferation of five HER2-amplified cell lines.
Showed potent inhibitory activities against cancer cell lines with HER2 amplification. |
Western Blot Analysis[1] | Cell Line: | SK-BR-3 cells | | Concentration: | 30-300 nM | | Incubation Time: | 3 and 48 hours | | Result: | Showed sustained inhibition of HER2, HER3, AKT and ERK phosphorylation. |
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体内研究
(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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 125 mg/mL(247.73 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9818 mL | 9.9092 mL | 19.8185 mL | | 5 mM | 0.3964 mL | 1.9818 mL | 3.9637 mL | | 10 mM | 0.1982 mL | 0.9909 mL | 1.9818 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.12 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.12 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.12 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.12 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.12 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.12 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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