EAI045

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Chemical Structure| 1942114-09-1 同义名 : -
CAS号 : 1942114-09-1
货号 : A105328
分子式 : C19H14FN3O3S
纯度 : 97%
分子量 : 383.396
MDL号 : MFCD30187871
存储条件：

Pure form Sealed in dry,2-8°C

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

DMSO: 105 mg/mL(273.87 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
动物实验配方：
生物活性
靶点

  • mutant EGFR
描述 EAI045 is an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild type receptor. It inhibited cellular p-EGFR-Y1173 with IC50 values of 2nM, 163nM and >10μM for H1975 (L858R T790M), H3255 (L858R) and HaCaT (WT), respectively. It almost completely depleted p-EGFR-Y1068 at concentration of 20μM in NIH-3T3 cells expressing L858R/T790M EGFR. But it is not effective in blocking EGFR-driven proliferation in cells as a single agent due to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state. Combination with cetuximab which blocks EGFR dimerization could potentiate the effect of EAI045 on mouse models of lung cancer driven by L858R/T790M EGFR and by L858R/T790M/C797S EGFR, a mutant that is resistant to all currently available EGFR TKIs[2].
作用机制 EAI045 binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of EGFR. EAI045 is an allosteric inhibitor, which distinguished it from current EGFR TKIs target the ATP-site of the kinase.[2]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.61mL

0.52mL

0.26mL

13.04mL

2.61mL

1.30mL

26.08mL

5.22mL

2.61mL
参考文献

[1]Jia Y, Yun CH, et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 Jun 2;534(7605):129-32.

[2]Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, Xu C, Rhee K, Chen T, Zhang H, Palakurthi S, Jang J, Lelais G, DiDonato M, Bursulaya B, Michellys PY, Epple R, Marsilje TH, McNeill M, Lu W, Harris J, Bender S, Wong KK, Jänne PA, Eck MJ. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 Jun 2;534(7605):129-32. doi: 10.1038/nature17960. Epub 2016 May 25. PMID: 27251290; PMCID: PMC4929832.