  Starting from the lead structure we have identified in our previous works, we
are extending our insight understanding of its potential inhibitory effect
against both EGFR and HER2 receptors. Herein and using extended molecular
dynamic simulations and different scoring techniques, we are providing
plausible explanations for the observed inhibitory effect. Also, we are
comparing the binding mechanism in addition to the dynamics of binding with two
other approved inhibitors against EGFR (Lapatinib) and HER2 (SYR). Based on
this information, we are also designing and in silico screening new potential
inhibitors sharing the same scaffold of the lead structure. We have chosen the
best scoring inhibitor for additional in silico investigation against both the
wild-type and T790M mutant strain of EGFR. It seems that certain substitution
pattern guarantees the binding to the conserved water molecule commonly
observed with kinase crystal structures. Also, the new inhibitors seem to form
a stable interaction with the mutant strain as a direct consequence of their
enhanced ability to form additional interactions with binding site residues.
