NDT 9513727 is a competitive antagonist of the C5a receptor (C5aR; IC50 = 11.6 nM for human recombinant receptors) that has inverse agonist activity in a GTPγ[35S] assay. It is selective for human recombinant over rat and mouse recombinant C5aRs (IC50 = >10 μM for both) but does have activity at macaque and gerbil receptors (IC50s = 7.3 and 6.4 nM, respectively). NDT 9513727 inhibits degranulation in U937 cells stimulated with C5a (IC50 = 7.1 nM). It also prevents neutropenia induced by human recombinant C5a in gerbils (ED50 = 2.2 mg/kg) and in cynomolgus macaques when administered at doses of 5 and 25 mg/kg.
NDT 9513727 is a selective, and potent inverse agonist of the human C5aR. NDT 9513727 has been shown to effectively inhibit C5a-induced neutropenia in gerbil and cynomolgus macaque in vivo. These results suggest that NDT 9513727 is a promising candidate for the treatment of human inflammatory diseases.
