DG-051 is a potent, orally bioavailable leukotriene A4 hydrolase (LTA4H) inhibitor (Kd = 25 nM; IC50 = 47 nM), the enzyme that catalyzes the rate-determining step in the synthesis of LTB4 . However, it also inhibits the aminopeptidase activity of LTA4H with IC50 values of 72 and 150 nM when tested using the substrates L-alanine p-nitroanaline and prolyl-glycyl-proline peptide , respectively, potentially leading to PGP accumulation in vivo. DG-051 does not show any inhibitory activity against a panel of more than 50 additional aminopeptidases, ion channels, or HERG.
References:
[1].Sandanayaka, V., Mamat, B., Mishra, R.K., et al. Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis J. Med. Chem. 53(2), 573-585 (2010).
[2]. Low, C.M., Akthar, S., Patel, D.F., et al. The development of novel LTA4H modulators to selectively target LTB4 generation Sci. Rep. 7, 44449 (2017).