Aerpio’s Tie2 activators target VE-PTP which is the most downstream negative regulator of Tie2 activation. VE-PTP limits Tie2 pathway signaling by catalytically removing phosphate groups that are required for activation of downstream signaling molecules. Razuprotafib (aka AKB-9778) is a potent and selective small molecule inhibitor of the catalytic activity of VE-PTP. VE-PTP inhibition with Razuprotafib restores Tie2 activation irrespective of the presence of Angpt1 or Angpt2, the Tie2 agonist and context dependent antagonist ligand, respectively.
Aerpio’s biologic Tie2 activators bind the extracellular domain of VE-PTP, possibly blocking its access to Tie2 or triggering its removal and degradation from the cell surface. Similar to razuprotafib, ARP-1536, a humanized VE-PTP monoclonal antibody, restores Tie2 activation irrespective of the presence of Angpt1 or Angpt2.