Pepstatin A #98806

Pepstatin A is a low molecular weight inhibitor of aspartyl proteases, including pepsin, renin, cathepsin D and cathepsin E (1). Cathepsin D is a ubiquitously expressed lysosomal aspartyl protease involved in the normal degradation of proteins; dysregulation of cathepsin D plays a role in neuronal degradation and malignant transformation. Cathespin D is highly expressed in triple-negative breast cancer (TNBC) cells. Pepstatin A treatment induced apoptosis and autophagy while reducing the proliferation, invasion, and migration of TNBC cells (2). Increased expression and leakage of lysosomal cathepsin D is associated with cardiomyocyte death related to hyperglycemia. Treatment with Pepstatin A markedly diminished high glucose-induced cardiomyocyte death (3). Pepstatin A treatment of osteoclast cells suppressed receptor activator of NF-κB ligand (RANKL)-induced differentiation to mononuclear osteoclast cells by blocking NFATc1 expression and inhibiting ERK signaling (4). Pepstatin A also inhibits human immunodeficiency virus (HIV) protease (5). Pepstatin A treatment of HIV-infected H9 cells decreased the level of HIV core antigen in the culture medium (6).