SLV338

SLV338 is a novel small molecule drug that acts as a dual inhibitor of endothelin-converting enzyme 1 (ECE-1) and neutral endopeptidase (NEP, also known as neprilysin). By inhibiting both ECE-1 and NEP, SLV338 targets two key enzymes involved in cardiovascular and fibrotic processes. ECE-1 is responsible for the production of endothelin-1, a potent vasoconstrictor and profibrotic mediator, while NEP degrades natriuretic peptides that have diuretic, vasodilatory, and antifibrotic effects. In preclinical studies using rat models of renovascular hypertension (2-kidney, 1-clip), SLV338 demonstrated the ability to prevent cardiac remodeling—including normalization of cardiac fibrosis and hypertrophy—without affecting blood pressure. These cardioprotective effects were comparable to those produced by losartan but occurred independently of blood pressure reduction. The mechanism appears at least partially mediated via suppression of cardiac transforming growth factor-beta 1 expression[4][5][6][7][8].