Millennium's new ACE in the hole

Millennium Pharmaceuticals Inc. has identified a homolog of angiotensin converting enzyme that the company said is not inhibited by marketed ACE inhibitors and may represent a novel target to treat hypertension and chronic heart failure (CHF). But since its function is unknown, it is not yet clear how useful the homolog will be as a therapeutic target.

MLNM last week published in Circulation Research the identification of ACE-related carboxypeptidase (ACE2), which it said is the first known human homolog of ACE. Like ACE, ACE2 uses the 10-amino acid angiotensin I (AngI) peptide as a substrate. However, while ACE produces the 8-amino acid vasoconstrictor angiotensin II (AngII), ACE2 produces a 9-amino acid peptide that can be cleaved into yet smaller peptides by ACE and other enzymes. However, ACE cannot generate AngII from the 9-amino acid peptide. ...