Updated project metadata. Ca2+/calmodulin-dependent protein kinase II alpha (CaMK2A) is an emerging drug target incerebral ischemia for which limited therapeutic options exist. Here we show that small-molecule analogs of the brain metabolite gamma-hydroxybutyric acid (GHB) afford neuroprotection via interaction specifically with the CaMK2A hub domain. Identification of CaMK2A as the GHB analog target was achieved by homogenate photoaffinity labeling followed by quantitative proteomics