Pro-B-type natriuretic peptide (proBNP) (proBNP)

Pro-B-type natriuretic peptide (proBNP) is a 108-amino acid precursor protein synthesized and secreted by cardiomyocytes, primarily in the ventricles, in response to increased cardiac wall stress and volume overload. It undergoes proteolytic processing at a specific N-terminal cleavage sequence (typically between Arg76 and Ser77) by enzymes such as furin and corin to produce the biologically active 32-amino acid B-type natriuretic peptide (BNP) and the inactive 76-amino acid N-terminal fragment (NT-proBNP). This cleavage process is a critical regulatory step in cardiovascular physiology, as mature BNP exerts potent vasodilatory, natriuretic, and diuretic effects to counteract heart failure progression. In clinical practice, proBNP and its cleavage products serve as gold-standard biomarkers for the diagnosis, prognosis, and management of heart failure. While proBNP itself is not a direct therapeutic target, the enzymes that process it and the pathways that degrade its active products (such as neprilysin) are major focuses of cardiovascular drug development, exemplified by the use of neprilysin inhibitors to augment the natriuretic peptide system.

Other names

N-terminal pro-B-type natriuretic peptideNT-proBNPBNP precursorB-type natriuretic peptide precursorproBNP(1-108)Gamma-brain natriuretic peptide

Sacubitril inhibits neprilysin, the enzyme responsible for degrading the active cleavage product (BNP), thereby increasing its circulating levels and therapeutic effects.