Inhibition of the angiotensin II type 2 receptor AT₂R is a novel therapeutic strategy for glioblastoma.

ABSTRACT: Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT₂R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT₂R. We repurposed EMA401, an AT₂R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT₂R-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity. The crystal structure of AT₂R bound to EMA401 was determined and revealed the receptor to be in an active-like conformation with helix-VIII blocking G-protein or β-arrestin recruitment. The architecture and interactio

SUBMITTER: Perryman R 

PROVIDER: S-EPMC9371711 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature