Pelitinib

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Chemical Structure| 257933-82-7 同义名 : EKB-569; WAY-EKB 569; WAY-172569
CAS号 : 257933-82-7
货号 : A111899
分子式 : C24H23ClFN5O2
纯度 : 99%+
分子量 : 467.92
MDL号 : MFCD09837868
存储条件：

Pure form Keep in dark place, inert atmosphere, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(53.43 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • EGFR/ErbB1

    EGFR, IC50:38.5 nM

  • HER2/ErbB2

    ErbB2, IC50:1.255 μM
描述 EGFR is a member of epidermal growth factor receptor (HER) family. It is a tyrosine kinase that participates in the regulation of cellular homeostasis. EGFR gene mutations and protein overexpression can both activate pathways (Protein Tyrosine Kinase/RTK). Pelitinib (EKB-569) is an irreversible EGFR inhibitor by inhibiting phosphorylation. It can also slightly inhibit SRC, MEK / ERK and erbB2. The inhibitory effect of Pelitinib on EGFR was higher than that of Src, MEK/ERK, Cdk4, c-Met, Raf and ErbB2. The IC50 for EGFR is 32-fold lower than the IC50 for ErbB2. The IC50s of Pelitinib in inhibiting NHEK, A431, MDA-468 cells proliferation were 61, 125 and 260 nM, respectively [3]. The result of in-cell western assay showed that Pelitinib inhibited endogenous total cellular tyrosine and endogenous ERK1/2 phosphorylation in a dose-dependent manner in A431 cells. Pelitinib at 1000 nM can inhibit EGFR and ERK phosphorylation significantly after 60 min incubation [4]. In vitro studies determined that Pelitinib at 100nM and 1,000nM inhibited circa 70% SS1-induced pERK1/2 relative to untreated SS1-stimulated in A431 cells. In vivo , studies showed that Pelitinib treatment resulted in a significant reduction (p < 0.05) in glandular herniations which were present in two of eight (25%) of H. pylori-infected Pelitinib treated gerbils [5].
作用机制 Pelitinib is an irreversible EGFR inhibitor by inhibiting phosphorylation.
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00072748 Colorectal Neoplasms ... 展开 >> Colonic Neoplasms Rectal Neoplasms 收起 << Phase 2 Completed - -
NCT00098501 Unspecified Adult Solid Tumor,... 展开 >> Protocol Specific 收起 << Phase 1 Completed - United States, Minnesota ... 展开 >> Mayo Clinic Rochester, Minnesota, United States, 55905 收起 <<
NCT00067548 Non-Small-Cell Lung Carcinoma ... 展开 >> Carcinoma, Non-Small Cell Lung Lung Neoplasms 收起 << Phase 2 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.14mL

0.43mL

0.21mL

10.69mL

2.14mL

1.07mL

21.37mL

4.27mL

2.14mL
参考文献

[1]Nunes M, Shi C, Greenberger LM. Phosphorylation of extracellular signal-regulated kinase 1 and 2, protein kinase B, and signal transducer and activator of transcription 3 are differently inhibited by an epidermal growth factor receptor inhibitor, EKB-569, in tumor cells and normal human keratinocytes. Mol Cancer Ther. 2004 Jan;3(1):21-7.

[2]Torrance CJ, Jackson PE, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med. 2000 Sep;6(9):1024-8.

[3] Torrance CJ, Jackson PE, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med. 2000 Sep; 6(9):1024-8

[4] Du Y, Danjo K, et al. In-Cell Western analysis of Helicobacter pylori-induced phosphorylation of extracellular-signal related kinase via the transactivation of the epidermal growth factor receptor. Microbes Infect. 2007 Jun; 9(7):838-46

[5] Crabtree JE, Jeremy AH, et al. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo. Pathogens. 2013 Oct 14; 2(4):571-90