aloxistatin

**Aloxistatin (E-64d)** is a synthetic, cell-permeable, irreversible inhibitor of cysteine proteases, derived as the ethyl ester of E-64c to enable membrane penetration and intracellular hydrolysis to the active form. It covalently modifies the active site thiol group of target proteases, primarily inhibiting calpains (calcium-dependent proteases) and cathepsins (B, F, H, K, L), with reported IC50 values around 0.5–1 μM for calpain. Widely used in research for autophagy studies (blocks autophagic cargo degradation, often combined with pepstatin A), apoptosis, platelet aggregation inhibition, and viral entry (e.g., SARS-CoV-2, MERS-CoV via cathepsin L inhibition). It has shown preclinical efficacy in models of traumatic brain injury, Alzheimer's disease (reduces amyloid-β via cathepsin B inhibition), muscular dystrophy, spinal cord injury, stroke, epilepsy, and prion disease, with prior safe use in humans but no successful clinical approval for specific indications.

Other names

loxistatin