In-silico designing of an inhibitor against mTOR FRB domain: Therapeutic implications against breast cancer

Abstract

Worldwide breast cancer causes significant fatalities in women. The effective therapeutic solution for treating the disease is using new and probable antagonistic biologically available ligands as anticancer drugs. To identify a successful therapeutic approach, the scientific community is now interested in creating novel ligands that in the future may be used as anticancer drugs. The mechanistic target of rapamycin (mTOR) is a protein kinase connected to several processes governing immunity, metabolism, cell development, and survival. The proliferation and metastasis of tumors have both been linked to the activation of the mTOR pathway. Female breast cancer represents about 15.3% of all new cancer cases in the U.S. alone and is frequently diagnosed among women aged 55 to 69 years. Given that the P13K/AKT/mTOR pathway is one of the most often activated in cancer, much attention has been paid to its resistance as a novel oncological treatment approach. mTOR/FRB Domain’s recruitment cleft as, well as substrate recruitment mechanism, was targeted using a structural-based approach. A series of selective inhibitory small molecules have been designed and screened for the best inhibiting target binding triad of the FRB Domain with better ADME and no detectable toxic effects.