A cell-permeable aminopyrimidine compound that acts as potent, ATP-competitive, and highly selective GSK-3 inhibitor (IC₅₀ = 10 and 6.7 nM against GSK-3α and GSK-3β, respectively). CHIR99021 exhibits little to no activity toward 46 other enzymes (IC₅₀>8.8 µM against 20 kinases and K_ι ≥5 µM against 23 non-kinase enzymes) and shows only weak binding to 22 pharmacologically relevant receptors (K_d ~4 µM). CHIR99021 is orally available and is shown to effectively improve glucose metabolism in both murine and rat type 2 diabetes models in vivo.