Bioinformatics, chemoinformatics, and pharmainformatics analysis of HER2/HSP90 dual-targeted inhibitors

Heat shock protein 90 (HSP90) and human epidermal growth factor receptor 2 protein (HER2) are involved in several signal pathways for cancer cell proliferation. I focused on these two hallmarkers to design the dual-targeted inhibitors for cancer therapy. The comparative molecular field analysis (CoMFA) and pharmacophore analysis were employed for generating the predictive models. According the leave-one out (LOO) cross-validation, the CoMFA models obtained the significant r2 values of 0.986 and 0.982 for HSP90 and HER2, respectively. The contour maps of both targets indicated that there were amount of similar bulky favors area. Besides, the cost difference of pharmacophore models was 48.539 for 70% correlation with the experiment. At the C2 position of the benzene ring, the HER2 model was more favor of steric bulky than HSP90. Contrast to HER2 model, the room which is near pent-4-ynyl group was more favor of steric bulky for HSP90 model. This study provided the significant CoMFA models and pharmacophore features for designing the HER2/HSP90 dual-targeted inhibitors.