Small Molecule Inhibitors of the PCSK9·LDLR Interaction.

ABSTRACT: The protein-protein interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) is a relatively new, and extremely important, validated therapeutic target for treatment and prevention of heart disease. Experts in the area agree that the first small molecules to disrupt PCSK9·LDLR would represent a milestone in this field, yet few credible leads have been reported. This paper describes how side-chain orientations in preferred conformations of carefully designed chemotypes were compared with LDLR side chains at the PCSK9·LDLR interface to find molecules that would mimic interface regions of LDLR. This approach is an example of the procedure called EKO (Exploring Key Orientations). The guiding hypothesis on which EKO is based is that g

SUBMITTER: Taechalertpaisarn J 

PROVIDER: S-EPMC6404525 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature