Aminopeptidase P (XPNPEP) (APP)

Aminopeptidase P (APP) is a specialized metalloaminopeptidase family, including cytosolic (XPNPEP1) and membrane-bound (XPNPEP2) isoforms, that specifically cleaves the N-terminal amino acid from peptides where the second residue is proline (X-Pro motifs). This specificity makes it a critical regulator of bioactive peptides such as bradykinin, which contains an N-terminal Arg-Pro sequence, and other proline-rich signaling molecules. In the context of oncology, APP is considered a tumor-associated enzyme because it is often overexpressed in various cancers and plays a role in promoting angiogenesis and tumor growth by modulating the local peptide environment. Therapeutic strategies targeting APP involve the use of small-molecule inhibitors like apstatin to disrupt these pro-tumorigenic pathways. However, inhibition of APP, particularly the membrane-bound form, is associated with a significant risk of life-threatening angioedema due to the accumulation of bradykinin, presenting a major safety challenge for drug development.

Other names

X-Pro aminopeptidaseXaa-Pro aminopeptidaseCytosolic aminopeptidase P (XPNPEP1)Membrane-bound aminopeptidase P (XPNPEP2)Mitochondrial aminopeptidase P (XPNPEP3)Proline-specific aminopeptidase

Inhibition of the enzyme's catalytic activity to prevent the degradation of bioactive peptides like bradykinin or to inhibit tumor-associated angiogenesis and proliferation.