Dipeptidyl peptidase 3 (DPP3) (DPP3)

Dipeptidyl peptidase 3 (DPP3) is a highly conserved, 83-kDa zinc-dependent metallopeptidase that primarily resides in the cytoplasm of various tissues [1, 8]. Under physiological conditions, it functions as an aminopeptidase, cleaving dipeptides from the N-terminus of oligopeptides such as enkephalins and angiotensins, and it also plays a non-enzymatic role in the Keap1-Nrf2 antioxidant response pathway [11, 14]. However, during severe cellular injury or death, DPP3 is released into the bloodstream, where it is referred to as circulating DPP3 (cDPP3) [10, 13]. In the circulation, cDPP3 acts as a 'cardiac depressant factor' by rapidly degrading angiotensin II, a critical regulator of vascular tone and myocardial contractility [3, 12]. This uncontrolled degradation leads to a breakdown of the renin-angiotensin-aldosterone system (RAAS), resulting in refractory hypotension, cardiovascular collapse, and multi-organ failure [8, 14]. Consequently, cDPP3 has emerged as both a potent biomarker for mortality and a novel therapeutic target in conditions like cardiogenic and septic shock [4, 15]. Therapeutic strategies, such as the humanized monoclonal antibody procizumab (invobenitug), aim to neutralize cDPP3 to restore RAAS balance and stabilize hemodynamics in critically ill patients [3, 13].

Other names

Dipeptidyl aminopeptidase IIIDipeptidyl arylamidase IIIDipeptidyl peptidase IIIEnkephalinase BCirculating dipeptidyl peptidase 3cDPP3

Procizumab is a humanized monoclonal antibody that neutralizes circulating dipeptidyl peptidase 3 (cDPP3), thereby preventing the enzymatic degradation of angiotensin II and other bioactive peptides [3, 8]. This inhibition restores the balance of the renin-angiotensin-aldosterone system (RAAS), which stabilizes cardiovascular hemodynamics, improves myocardial contractility, and reverses organ dysfunction in patients with shock [12, 14].