A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy.

ABSTRACT: CC Chemokine Receptor 2 (CCR2) and its endogenous ligand CCL2 are involved in a number of diseases, including atherosclerosis. Several CCR2 antagonists have been developed as potential therapeutic agents, however their in vivo clinical efficacy was limited. In this report, we aimed to determine whether 15a, an antagonist with a long residence time on the human CCR2, is effective in inhibiting the development of atherosclerosis in a mouse disease model. First, radioligand binding assays were performed to determine affinity and binding kinetics of 15a on murine CCR2. To assess the in vivo efficacy, western-type diet fed apoE^-/- mice were treated daily with 15a or vehicle as control. Treatment with 15a reduced the amount of circulating CCR2⁺ monocytes and the size of the

SUBMITTER: Bot I 

PROVIDER: S-EPMC5427923 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature