Description
BMS 813160 is a dual antagonist of chemokine receptor 2 (CCR2) and CCR5 (IC
50s = 6.2 and 3.6 nM, respectively, in radioligand binding assays). It inhibits chemotaxis induced by the CCR2 ligand MCP-1 in THP-1 cells the CCR5 ligand MIP-1β in isolated peripheral T cells with IC
50 values of 0.8 and 1.1 nM, respectively. BMS 813160 inhibits peritoneal monocyte and macrophage infiltration in an hCCR-2 KI mouse model of thioglycolate-induced peritonitis, with 54% inhibition when administered at a dose of 50 mg/kg twice per day.
Uses
BMS-813160, a dual CCR2/CCR5 chemokine antagonist.
in vivo
BMS-813160 (10-160 mg/kg; p.o. twice a day for two days) inhibits the migration of inflammatory monocytes and macrophages in mouse thioglycollate-induced peritonitis model, and shows excellent oral bioavailability[2].
| Animal Model: | Human-CCR2 knock-in C57BL/6 male mice with thioglycollate injection[2] |
| Dosage: | 10, 50 and 160 mg/kg |
| Administration: | Oral gavage; 10-160 mg/kg twice a day; for two days |
| Result: | Dose-dependently reduced inflammatory monocyte and macrophage infiltration in the peritoneum. |
IC 50
CCR5: 3.6 nM (IC
50); CCR2: 6.2 nM (IC
50)
References
[1] De Souza, F.I., Zumiotti, A.V., and Da Silva, C.F. Neuregulins 1-α and 1-β on the regeneration the peripheral nerves[J]. Acta Ortop Bras.
[2] NORMAN P. A dual CCR2/CCR5 chemokine antagonist, BMS-813160 Evaluation of WO2011046916.[J]. Expert Opinion on Therapeutic Patents, 2011, 21 12: 1919-1924. DOI:
10.1517/13543776.2011.622750
