Ontology highlight
ABSTRACT:
SUBMITTER: Lintner NG
PROVIDER: S-EPMC5360235 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Lintner Nathanael G NG McClure Kim F KF Petersen Donna D Londregan Allyn T AT Piotrowski David W DW Wei Liuqing L Xiao Jun J Bolt Michael M Loria Paula M PM Maguire Bruce B Geoghegan Kieran F KF Huang Austin A Rolph Tim T Liras Spiros S Doudna Jennifer A JA Dullea Robert G RG Cate Jamie H D JH
PLoS biology 20170321 3
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demo ...[more]