SCREENING OF NOVEL INHIBITOR FOR HER2 INDUCED BREAST CANCER-AN INSILICO APPROACH

HER2 stands for Human Epidermal growth factor Receptor 2. Each normal breast cell contains copies of the HER2 gene coding for HER2 protein found on the cell surface, which helps normal cells grow.HER2+ breast cancer is characterized by over expression of this gene in breast cells which fosters the cell growth giving rise to breast tumors. Studies show that 20-25% of breast cancer patients have tumors that are HER2+ making it a significant target for breast cancer studies. Identification of effective, well tolerated HER2 inhibitors represents a rational chemo preventive strategy. Here I present a study on the 27 herbal HER2 targeted lead compounds and their potential binding affinity to HER2. Iressa and Lapatinib served as reference drugs. Lipinski’s rule of five was applied to all the herbal compounds to evaluate their drug likeness, pharmacological or biological activity. Depending on Lipenski’s rule, the molecules which were following the criteria for the same were subjected to energy minimization using MARVIN SKETCH and receptor-ligand interaction study using QUANTUM docking tool. Reference drugs were also subjected to the same studies. Silymarin showed good docking score in comparison with the reference drugs. After the docking step, Silymarin was subjected to binding site analysis in Q site Finder where the binding interaction with HER2 was clearly observed. Using ADME TOX analysis it was found that silymarin was showing lower Ames test value than the reference drugs. The high ligand binding affinity of silymarin to HER2 receptor introduce the prospects of its use in chemo preventive applications. Further animal studies needs to be done to confirm the exact role and mechanism of Silymarin as a cancer chemo preventive agent for breast cancer