DX600 is a potent and selective peptide inhibitor of angiotensin-converting enzyme 2 (ACE2; Kis = 2.8, 200, and 1,200 nM for recombinant, human, and murine ACE2, respectively).1,2 ACE2 is an enzyme that is cardioprotective and renoprotective.3 Inhibition of ACE2 with DX600 reduces in vitro vascular repair by CD34+ stem/progenitor cells and exacerbates myocardial injury and dysfunction in vivo.4,5
1.Huang, L., Sexton, D.J., Skogerson, K., et al.Novel peptide inhibitors of angiotensin-converting enzyme 2J. Biol. Chem.278(18)15532-15540(2003) 2.Joshi, S., Balasubramanian, N., Vasam, G., et al.Angiotensin converting enzyme versus angiotensin converting enzyme-2 selectivity of MLN-4760 and DX600 in human and murine bone marrow-derived cellsEur. J. Pharmacol.77425-33(2016) 3.Prada, J.A.H., Ferreira, A.J., Katovich, M.J., et al.Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agentsHypertension511312-1317(2008) 4.Singh, N., Joshi, S., Guo, L., et al.ACE2/Ang-(1-7)/Mas axis stimulates vascular repair-relevant functions of CD34+ cellsAm. J. Physiol. Heart. Circ. Physiol.309H1697-H1707(2015) 5.Song, B., Zhang, Z.-Z., Zhong, J.-C., et al.Loss of angiotensin-converting enzyme 2 exacerbates myocardial injury via activation of the CTGF-fractalkine signaling pathwayCirc. J.77(12)2997-3006(2013)