产品说明书

Poziotinib

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Chemical Structure| 1092364-38-9 同义名 : HM781-36B;NOV120101
CAS号 : 1092364-38-9
货号 : A719269
分子式 : C23H21Cl2FN4O3
纯度 : 98%
分子量 : 491.342
MDL号 : MFCD28044290
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 8 mg/mL clear

PO 0.5% CMC-Na 50 mg/mL suspension

生物活性
靶点

  • EGFR/ErbB1

    HER1, IC50:3.2 nM

  • HER2/ErbB2

    HER2, IC50:5.3 nM

  • ErbB4

    HER4, IC50:23.5 nM

  • HER2

    HER2, IC50:5.3 nM
描述 EGFR (epidermal growth factor receptor) family consists of four members that belong to the ErbB lineage of proteins (ErbB1 - 4) with an external domain that binds activating ligands, such as EGF, and is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. Poziotinib is an irreversible pan-ErbB inhibitor with IC50 values of 3.2 nM, 5.3 nM and 23.5 nM for ErbB1, ErbB2 and ErbB4 (measured by in vitro kinase assays), respectively. Compared to other HER family TKIs like Lapatinib, Cl-1033, Gefitinib and BIBW-2992, Poziotinib has potent growth inhibitory activity against ErbB2 amplified gastric cancer cells, including SNU-1, 5, 16, 216, 484, 601, 620, 638, 668, 719, N87 and AGS, along with more potent inhibition on the phosphorylation of HER family and the key components of downstream signaling cascades such as STAT3, AKT and ERK, and also induces G1 cell cycle arrest and apoptosis with activation on the mitochondrial pathway. In vivo study showed that Poziotinib (0.5 mg/kg) exerted a synergistic effect with 5-FU (50 mg/kg) in a nude mouse bearing N87 human gastric cancer xenograft model[1].
作用机制 Poziotinib can covalently bind and inhibit mutant EGFR and HER2 kinases[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.04mL

0.41mL

0.20mL

10.18mL

2.04mL

1.02mL

20.35mL

4.07mL

2.04mL
参考文献

[1]Nam HJ, Kim HP, et al. Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer. Cancer Lett. 2011 Mar 28;302(2):155-65.

[2]Cha MY, Lee KO, et al. Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models. Int J Cancer. 2012 May 15;130(10):2445-54.

[3]Kim E, Kim H, et al. Metabolite identification of a new tyrosine kinase inhibitor, HM781-36B, and a pharmacokinetic study by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2013 Jun 15;27(11):1183-95.