Docking and molecular dynamics studies of new potential inhibitors of the human epidermal receptor 2

Abstract

Compounds similar to lapatinib and gefitinib have been investigated as potential inhibitors of the intracellular receptor tyrosine kinase (RTK) domain of the human epidermal receptor 2 (HER2), which is a promising molecular target to the drug design of new chemotherapies for breast, lung, ovarian and colorectal cancers. In this study, we have searched potential HER2 inhibitors used for treatment of other illnesses such as hepatitis, bacterial infections and sexual impotence screened in the DrugBank. The compounds selected were subjected to virtual screening docking in order to evaluate the main interactions between them and the RTK domain of HER2. The selected compounds were investigated by flexible docking, molecular dynamics studies and ΔG _bind calculations. The results suggest that antrafenine, saprisartan, reserpine, irinotecan and udenafil are potential candidates to inhibit the RTK domain of HER2.

Keywords:

• cancer
• HER2
• docking
• molecular dynamics
• virtual screening

Acknowledgements

The authors thank the Brazilian funding agencies CNPq (Grant No. 304187/2009-7), CAPES (Grant No. 02559/09-9) and FAPERJ (Grant Nos E-26/101.452/2010 and E-26-111.532/2008) for financial support. W.A.C. also thanks CNPq and the Fundação Estudar for financial support and fellowship. A.S.P. is recipient of the FAPERJ Young Scientist of Our State award.