NDT 9513727

NDT 9513727 is a potent, selective, orally active and competitive inverse agonist of the human C5aR (C5a receptor), with an IC50 of 11.6 nM. NDT 9513727 can be used for the research of human inflammatory diseases[1].

Signaling Pathways >> Immunology/Inflammation >> Complement System

Research Areas >> Inflammation/Immunology

IC50: 11.6 nM (human C5aR)[1]

NDT 9513727 inhibits C5a-stimulated responses, including guanosine 5'-3-O-(thio)triphosphate binding, Ca2+ mobilization, oxidative burst, degranulation, cell surface CD11b expression and chemotaxis in various cell types with IC50s from 1.1 to 9.2 nM, respectively[1].

NDT 9513727 (3-30 mg/kg; p.o.) exhibits a dose-dependent inhibition of hC5a-induced neutropenia[1]. NDT 9513727 exhibits moderate oral bioavailability (rat 73%, monkey 26%) and Cmax (rat 5.98 μM, monkey 830 nM) following oral administration (rat 50, monkey 25.2 mg/kg)[1]. NDT 9513727 exhibits moderate plasma elimination half-lives (rat 4.8, monkey 7.9 h) due to low plasma clearance (1.4 L/h/kg and 3.8 l/h/kg respectively) following oral administration (rat 50, monkey 25.2 mg/kg)[1]. Animal Model: Six-week-old Mongolian gerbils[1] Dosage: 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg Administration: Oral administration Result: Significantly inhibited hC5a-induced neutropenia at 3 mg/kg, 10 mg/kg, 30 mg/kg. Animal Model: Rat[1] Dosage: 50 mg/kg Administration: Oral administration Result: Oral bioavailability (73%), Cmax (5.98 μM), T1/2 (4.8 h). Animal Model: Monkey[1] Dosage: 25.2 mg/kg Administration: Oral administration Result: Oral bioavailability (26%), Cmax (830 nM), T1/2 (7.9 h).

[1]. Robbin M Brodbeck, et al. Identification and characterization of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a novel, orally bioavailable C5a receptor inverse agonist. J Pharmacol Exp Ther. 2008 Dec;327(3):898-909.