Simvastatin is an HMGCR (HMG-CoA reductase) inhibitor with anti-proliferative properties. This compound has been shown to modulate purified bovine pituitary 20 S proteasome via mild stimulation of chymotrypsin-like activity and inhibition of peptidylglutamylpeptide hydrolyzing activity. Mechanistic studies suggest that Simvastatin decreases CDK4 and CDK2 kinase activities and represses high glucose-induced Rho A (Rho GTPase)/p21 signaling in mesangial cells. Simvastatin also potentiates apoptosis in human myeloid leukemia cells via the suppression of TNF-induced NF-κB activation (IC50 ~ 13 µM).