Endothelin-converting enzyme 2 (ECE-2)

Endothelin-converting enzyme 2 is a zinc-dependent metalloprotease of the M13 family, localized mainly to intracellular compartments in neural and neuroendocrine tissues, with a preference for acidic pH and selective activity on peptide substrates[1][4][5]. It converts big endothelin-1 to the potent vasoconstrictor endothelin-1, processes regulatory neuropeptides such as neurotensin and opioid peptides, and degrades amyloid beta in the brain[1][2][3][5]. ECE-2 differs from its close homolog ECE-1 by its subcellular localization and pH optimum. ECE-2 plays a role in the biosynthesis of active peptides with differential receptor selectivity, and its upregulation has been implicated in Alzheimer’s disease and pain modulation[2][3]. Selective inhibition of ECE-2 can impact opioid signaling and is considered a relevant therapeutic target for diseases where peptide signaling is dysregulated[3][2].

Other names

ECE2Endothelin-converting enzyme-2Endothelin-converting enzyme 2 (human)EC 3.4.24.72

Direct inhibition (e.g., S136492 blocks ECE-2’s peptide-processing activity, impacting opioid signal resensitization). Reduction of endothelin-1 production (potentially affecting vasoconstriction and cerebral blood flow).