Drug Repurposing Screen Identifies Foxo1-Dependent Angiopoietin-2 Regulation in Sepsis.

ABSTRACT:

Objective

The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms.

Design

Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897).

Setting

Research laboratories of Hannover Medical School and Harvard Medical School.

Patients

Septic patients/C57Bl/6 mice and human endothelial cells.

Interventions

Food

SUBMITTER: Ghosh CC 

PROVIDER: S-EPMC4806531 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature