Endothelin-converting enzyme 1 (ECE-1) (ECE-1)

Endothelin-converting enzyme 1 (ECE-1) is a membrane-bound zinc metalloendopeptidase that processes the peptide precursor big endothelin into the biologically active endothelin-1 (ET-1), a potent vasoconstrictor and mitogen. ECE-1 exists as four isoforms (a–d), which share a catalytic domain but differ in their N-terminal domains, leading to distinct subcellular localizations—mainly plasma membrane and endosomes. While its best-characterized function is ET-1 production, ECE-1 also degrades several neuropeptides (substance P, bradykinin, CGRP, somatostatin) in endosomes, thereby influencing receptor recycling and re-sensitization in endothelial and neuronal cells. ECE-1 plays a key role in regulating cardiovascular physiology and is implicated in the pathophysiology of hypertension, cancer, and inflammation. Overexpression of ECE-1 in certain cancers (e.g., prostate, melanoma) is associated with more aggressive disease and drug resistance. ECE-1 can also be regulated by hypoxia-inducible factor (HIF), linking it to hypoxic responses in kidney and other tissues. Pharmacological targeting of ECE-1 (enzyme inhibitors) or downstream endothelin receptors (receptor antagonists) is under investigation for several clinical indications, although challenges remain regarding specificity and safety[1][3][5].

Other names

Endothelin converting enzyme 1ECE1Endothelin-1 converting enzymeEndothelin-1 converting enzyme 1Endothelinase

Inhibition — blocks the conversion of big endothelin to endothelin-1 (ET-1), reducing ET-1-mediated signaling and downstream effects (vasoconstriction, proliferation, angiogenesis). For disease states involving excess ET-1 (e.g., pulmonary hypertension, certain cancers), ECE-1 inhibitors aim to lower ET-1 production. Endothelin receptor antagonists (e.g., bosentan, macitentan, BQ788) target signaling downstream of ET-1.