Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury.

ABSTRACT: Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafen

SUBMITTER: Cruz SA 

PROVIDER: S-EPMC5879896 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature