Sapitinib (AZD-8931) , a reversible, ATP competitive inhibitor of EGFR(IC50=4 nM), ErbB2(IC50=3 nM) and ErbB3(IC50=4 nM), is more effective over Gefitinib or Lapatinib against NSCLC cell, 100-fold more specific for the ErbB family over MNK1 and Flt.

EGFR:4 nM, ErbB2:3 nM, ERB3:4 nM

Sapitinib对NSCLC和SCCHN细胞系表现出不同的活性。在具有EGFR激活突变的PC-9细胞上，Sapitinib显示出高灵敏度，其GI50为0.1 nM；而对NCI-1437细胞的活性较低，GI50超过10 μM。与lapatinib或gefitinib相比，Sapitinib在PE/CA-PJ41、PE/CA-PJ49、DOK及FaDu细胞中，对phospho-EGFR、phospho-erbB2和phospho-erbB3的抑制作用更强。[1]

Sapitinib在BT474c、Calu-3、LoVo、FaDu和PC-9异种移植瘤中显示出抗肿瘤活性。在急性处理后，Sapitinib能够降低BT474c异种移植瘤中的p-Akt、Ki67表达和p-ERK。Sapitinib还引起M30凋亡标记的诱导。此外，与gefitinib和lapatinib相比，Sapitinib在LoVo异种移植瘤中展现出更强的促凋亡效应。[1]

Isolated kinase assays: The intracellular kinase domains of human EGFR and erbB2 are cloned and expressed in the baculovirus/Sf21 system. The inhibitory activity of AZD8931 is determined with ATP at Km concentrations (0.4 mM for erbB2 and 2 mM for EGFR) using the ELISA method.

To determine the antiproliferative activity against cell lines grown in vitro, AZD8931 is tested in a panel of NSCLC and SCCHN cell lines. Cells are incubated for 96 hours with AZD8931 (0.001-10 μM). Viable cell number is determined by 4 hours of incubation with MTS Colorimetric Assay reagent and absorbance measured at 490 nm on a spectrophotometer. (Only for Reference)