IACS-13909 是一种有效的选择性的，具有口服活性的SHP2变构抑制剂，其IC50为 15.7 nM，Kd为 32 nM。与其他磷酸酶 (包括 SHP1) 相比，IACS-13909 对SHP2的选择性更高。IACS-13909 抑制受体酪氨酸激酶 (RTK)/MAPK 途径的信号传导，并具有抗癌作用。
| 生物活性 | IACS-13909 is a selective, potent and orally activeSHP2allosteric inhibitor with anIC50of 15.7 nM and aKdof 32 nM. IACS-13909 is more selective forSHP2than other phosphatases (including SHP1). IACS-13909 has antitumor activities and suppresses MAPK pathway signaling inreceptor tyrosine kinases(RTK)-dependent cancers[1]. |
| IC50& Target | IC50: 15.7 nM (SHP2)[1]
Kd: 32 nM (SHP2)[1] |
体外研究
(In Vitro) | IACS-13909 (10 nM-10 μM; 14 days) treatment potently suppresses the proliferation of wild-type SHP2 and KYSE-520 cells[1].
IACS-13909 (1-5 μM; 2 hours) treatment potently suppresses pERK and pMEK levels in wild-type SHP2 and KYSE-520 cells[1].
IACS-13909 potently suppresses the proliferation of both the parental cells and NCI-H1975 CS cells in a dose-dependent manner, with similar potency (GI50 ~1 μM). IACS-13909 (0.041-3.3 μM) suppresses pERK in NCI-H1975 CS cells in a dose-dependent manner[1].
Cell Proliferation Assay[1] | Cell Line: | Wild-type SHP2 and KYSE-520 cells | | Concentration: | 10 nM, 100 nM, 1 μM, 10 μM | | Incubation Time: | 14 days | | Result: | Potently suppressed the cell proliferation. |
Western Blot Analysis[1] | Cell Line: | Wild-type SHP2 and KYSE-520 cells | | Concentration: | 1 μM, 5 μM | | Incubation Time: | 2 hours | | Result: | Potently suppressed pERK and pMEK levels. |
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体内研究
(In Vivo) | IACS-13909 (70 mg/kg; oral administration; daily; for 21 days) treatment potently suppresses tumor growth in mice, with 100% tumor growth inhibition (TGI) observed following 21 days of dosing[1].
| Animal Model: | NSG mice (20-28 g) injected with KYSE-520 cells[1] | | Dosage: | 70 mg/kg | | Administration: | Oral administration; daily; for 21 days | | Result: | Potently suppressed tumor growth in mice. |
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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 : 10 mg/mL(26.51 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.6506 mL | 13.2531 mL | 26.5062 mL | | 5 mM | 0.5301 mL | 2.6506 mL | 5.3012 mL | | 10 mM | 0.2651 mL | 1.3253 mL | 2.6506 mL |
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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: ≥ 1 mg/mL (2.65 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (2.65 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 10.0 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。 *以上所有助溶剂都可在本网站选购。
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