NDT9513727 is a potent, selective and orally bioavailable C5a receptor inverse agonist with IC50 of 11.6 nM in radioligand binding assay.
NDT 9513727 exhibits potent activity in both gerbil and monkey lung membrane preparations (6.4 and 7.3 nM), but has minimal activity in rat, mouse, and dog lung preparations (>10 uM).
NDT 9513727 blocks hC5a-stimulated chemotaxis activity in human polymorphonuclear neutrophils and U937 cells with IC50 of 4.7 and 4.3 nM, respectively, inhibits C5a-stimulated responses, including guanosine 5'-3-O-(thio)triphosphate binding, Ca(2+) mobilization, oxidative burst, degranulation, cell surface CD11b expression and chemotaxis in various cell types with IC50 of 1.1-9.2 nM.
NDT 9513727 effectively inhibits C5a-induced neutropenia in gerbil and cynomolgus macaque in vivo.
