Mobocertinib (TAK-788) 是一种口服有效并且不可逆的EGFR/HER2抑制剂。Mobocertinib 能选择性地 (相较于野生型EGFR) 抑制含有EGFRex20ins的致癌突变体。Mobocertinib 可用于 NSCLC 的研究。
| 生物活性 | Mobocertinib (TAK-788) is an orally active and irreversibleEGFR/HER2inhibitor. Mobocertinib potently inhibits oncogenic variants containing activatingEGFRex20insmutations with selectivity over wild-typeEGFR. Mobocertinib can be used in NSCLC research[1][2]. |
| IC50& Target[1] | EGFR (WT) | EGFR exon 20 insertion | HER2 |
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体外研究
(In Vitro) | Mobocertinib (1.5 nM-10 μM; 7 days) inhibits LU0387 (NPH) cells with IC50of 21 nM[1].
Mobocertinib (2 h) potently inhibits EGFR with common activating mutations (HCC827 (D), HCC4011 (L)) or with a T790M mutation (H1975 (LT)) more potently than WT EGFR (A431 (WT))[1].
Mobocertinib (0.1 nM-1 μM; 6 h) inhibits pEGFR and pERK1/2 in CUTO14 (ASV) cells[1].
Mobocertinib (0.3 nM-1 μM; 6 h) inhibits EGFR and downstream signaling[1].
Mobocertinib (0.01, 0.1 and 1 μM; 6 h) inhibits HER2 signaling in H1781 (HER2 Exon 20G776>VC), Ba/F3 (HER2 exon 20YVMA) cells[2].
Cell Viability Assay[1] | Cell Line: | LU0387 (NPH) cells | | Concentration: | 1.5 nM-10 μM | | Incubation Time: | 7 days | | Result: | Showed good inhibition activity for LU0387 (NPH) cells with IC50of 21 nM. |
Cell Viability Assay[1] | Cell Line: | A431 (WT), HCC827 (D), HCC4011 (L), H1975 (LT) cells | | Concentration: | | | Incubation Time: | 2 h | | Result: | Inhibited EGFR with common activating mutations of HCC827 (D), HCC4011 (L) cells and T790M mutation of H1975 (LT) with IC50s of 4, 1.3 and 9.8 nM respectively, which more potently than WT EGFR (A431 (WT); IC50of 35 nM). |
Western Blot Analysis[1] | Cell Line: | CUTO14 (ASV) cells | | Concentration: | 0.1 nM-1 μM | | Incubation Time: | 6 h | | Result: | Robustly inhibited EGFR signaling, reaching 80% and 100% inhibition of phosphorylated EGFR (pEGFR) at concentrations of 100 nM and 1 μM, respectively. |
Western Blot Analysis[1] | Cell Line: | HCC827 (D), HCC4011 (L), H1975 (LT) cells | | Concentration: | 0.3 nM-1 μM | | Incubation Time: | 6 h | | Result: | Potently inhibited EGFR and downstream signaling in HCC827 (D), HCC4011 (L) and H1975 (LT) cells. |
Western Blot Analysis[2] | Cell Line: | H1781 (HER2 Exon 20G776>VC), Ba/F3 (HER2 exon 20YVMA) cells | | Concentration: | 0.01, 0.1 and 1 μM | | Incubation Time: | 6 h | | Result: | Inhibited HER2 signaling in H1781 and Ba/F3-HER2 exon 20YVMAmutant cells at 0.1 μM with significantly decreased phosphorylations of HER2, AKT, and ERK1/2 in a dose-dependent manner. |
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体内研究
(In Vivo) | Mobocertinib (3, 10, 30 mg/kg; p.o.; once daily for 20 days) significantly induces tumor growth inhibition[1].
| Animal Model: | Female Athymic Nude-Foxn1numice (human NSCLC H1975 LT tumor model)[1]. | | Dosage: | 3, 10, 30 mg/kg | | Administration: | Oral; once daily for 20 days. | | Result: | Decreased the mean tumor volume by 44% and 92% when at 3 mg/kg and 10 mg/kg, respectively, relative to the tumor size of vehicle group.
Induced a 76% tumor regression relative to the pretreatment tumor size at 30 mg/kg. |
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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 : 25 mg/mL(42.68 mM;ultrasonic and warming and heat to 80℃) 配制储备液 | 1 mM | 1.7074 mL | 8.5368 mL | 17.0736 mL | | 5 mM | 0.3415 mL | 1.7074 mL | 3.4147 mL | | 10 mM | 0.1707 mL | 0.8537 mL | 1.7074 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: ≥ 2.5 mg/mL (4.27 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.27 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 1.25 mg/mL (2.13 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (2.13 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 12.5 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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