Mode of Action

General Mechanisms

PETIR™ peptidase inhibitors target two enzymes that are over-expressed on immune cells and other cell systems in cases of inflammation.
The target peptidases belong to Aminopeptidase N (APN, CD13) and Dipeptidylpeptidase IV (DPIV, CD26) families.

These peptidases are present on immune cells particularly after activation in case of inflammation. Thus, the therapeutic effects are achieved via cutting off pathologically higher enzyme activity levels.

Inhibition of these peptidases results in a growth arrest of activated lymphocytes, keratinocytes, sebocytes and fibroblasts, as well as the activation of natural regulatory T cells (Tregs).
In parallel, the release of anti-inflammatory cytokines such as TGF-β1 and IL-35 is induced.
These effects are mediated via different signalling pathways.

Remarkably, also Th17 cells - the main pathogenic population of autoimmune disorders- are strongly suppressed by PETIR™ compounds.

Cellular DPIV is capable to inactivate the immunosuppressive Neuropeptide Y (NPY), which is a strong inducer of another immunosuppressive cytokine, TGF-ß1. Consequently, those inhibitors of cellular DPIV are compounds with strong immunosuppressive and neuroprotective functions, in that they protect the immunosuppressive NPY and other anti-inflammatory cytokines (VIP) as well as mediate the induction of TGF-ß1 and BDNF.
In summary, PETIR™ act by five general mechanisms:

  • Inhibition of DNA synthesis and proliferation of inflammatory cells
  • Reduction of inflammatory cytokines (Th1, Th2 and Th17)
  • Activation of CD4+CD25+ Treg cells (suppressor cells) and
  • Induction of anti-inflammatory neuroprotective cytokines (TGF-β1, IL-35, BDNF)
  • Prevention of breakdown of neuroprotective mediators (NPY, VIP, PACAP)