Dacomitinib (Synonyms:达克替尼; PF-00299804; PF-299804)
目录号 : KM6888 CAS No. : 1110813-31-4 纯度 : 98%

Dacomitinib (PF-00299804) 是一种特异,不可逆的 ERBB 家族抑制剂,作用于 EGFR,ERBB2 和 ERBB4 的 IC50 分别为 6 nM,45.7 nM 和 73.7 nM。

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生物活性

Dacomitinib (PF-00299804) is a specific and irreversible inhibitor of the ERBB family of kinases with IC50s of 6 nM, 45.7 nM and 73.7 nM for EGFR, ERBB2, and ERBB4, respectively.

体外研究

Dacomitinib (PF00299804) effectively inhibits the in vitro kinase activity of wild-type EGFR (IC50=6 nM)with similar efficacy. Dacomitinib also effectively inhibits wild-type ERBB2 with IC50 of 45.7 nM. In H441, an IC50 is reached with Dacomitinib but only at a very high concentration (4 μM) and likely reflects off-target effects. In cell lines wild-type for both EGFR and K-ras (H322, H1819, and Calu-3), ZD1839 and Dacomitinib both effectively inhibit growth of H1819 and Calu-3 cells but not of H322 cells. Dacomitinib is a pan-ERBB inhibitor and most EGFR mutant cell lines express multiple ERBB family members, the effects on EGFR phosphorylation could potentially be indirect. Dacomitinib inhibits EGFR phosphorylation in all of the different EGFR T790M proteins whereas ZD1839 is ineffective even at 10 μM. In the NIH3T3 cells, phosphorylation of EGFR L858R/T790M is completely inhibited by 1 nM Dacomitinib, whereas 100 nM or greater is required to inhibit EGFR WT/T790M or Del/T790M. The HER2-amplified cell lines are most sensitive to growth inhibition by Dacomitinib (IC50<1 μM in 14 of 16 lines; 87.5%) as compared with 5 of 28 (17.9%) of HER2-nonamplified lines (excluding immortalized lines).

体内研究

To evaluate the efficacy of Dacomitinib, xenografts in nu/nu mice are generated using HCC827 GFP and HCC827 Del/T790M cells and treated the mice with Dacomitinib. Dacomitinib (10 mg/kg/d by daily oral gavage) effectively inhibits the growth of HCC827 GFP xenografts. In contrast, HCC827 Del/T790M xenografts are resistant to ZD1839, whereas Dacomitinib treatment is substantially more effective at inhibiting growth of this xenograft model.

分子式
C24H25ClFN5O2
分子量
469.94
CAS号
1110813-31-4
中文名称
达克替尼;达克米替尼
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
溶解性数据
In Vitro: 

DMSO : 40 mg/mL (85.12 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1279 mL 10.6397 mL 21.2793 mL
5 mM 0.4256 mL 2.1279 mL 4.2559 mL
10 mM 0.2128 mL 1.0640 mL 2.1279 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°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 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 (5.32 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.32 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% (20% SBE-β-CD in saline)

    Solubility: 2.5 mg/mL (5.32 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.5 mg/mL (5.32 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 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: ≥ 2.5 mg/mL (5.32 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.32 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

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科研文献
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