Design, Synthesis, and Docking Studies of New Torin2 Analogs as Potential ATR/mTOR Kinase Inhibitors.

ABSTRACT: Targeting DNA damage and response (DDR) pathway has become an attractive approach in cancer therapy. The key mediators involved in this pathway are ataxia telangiectasia-mutated kinase (ATM) and ataxia telangiectasia-mutated, Rad3-related kinase (ATR). These kinases induce cell cycle arrest in response to chemo- and radio-therapy and facilitate DNA repair via their major downstream targets. Targeting ATP-binding site of these kinases is currently under study. Torin2 is a second generation ATP competitive mTOR kinase inhibitor (EC₅₀ = 250 pmol/L) with better pharmacokinetic profile. Torin2 also exhibits potent biochemical and cellular activity against ATM (EC₅₀ = 28 nmol/L) and ATR (EC₅₀ = 35 nmol/L) kinases. In this study, eight new Torin2 analogs were desi

SUBMITTER: Shaik A 

PROVIDER: S-EPMC6102578 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature