Figure 2.

The selection procedure for the IAP inhibitor. (a) We first used LBDS (Ligand-Based Docking System) and SBDS (Structure-Based Docking System) to develop the small-molecule Smac-mimetic IAP antagonist, which was designed to bind to the BIR3 domain of IAP family members, as well as EGFR, and then screened compounds based on the biological effect by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay. (b) The structure of HM90822B. (c) The expression levels of IAPs were analyzed after treatment with HM90822B in NSCLC cells. A549, Beas2B, H23, H322 and H522 cells were incubated in the presence of the indicated concentrations of HM90822B for 3 days, and PC9, HCC827, H1975 or PC9GR cells were incubated in the presence of the indicated concentrations of HM90822B for 1 day. Whole cell lysates (30 μg) were analyzed by western blotting with antibodies against XIAP, survivin, cIAP1, cIAP2, EGFR and β-actin