RS102895 hydrochloride acts as a strong antagonist of CCR2, demonstrating an IC50 value of 360 nM, while exhibiting no influence on CCR1. This compound further exerts inhibitory effects on human α1a and α1d receptors, along with the 5HT1a receptor in rat brain cortex cells, showcasing IC50 values of 130, 320, and 470 nM, respectively. It effectively diminishes activity in both the wild type and D284N variant of the MCP-1 receptor, with IC50 figures of 550 nM and 568 nM, respectively, and exhibits a weaker inhibition against the D284A variant of MCP-1 receptor (IC50 of 1892 nM). It displays no impact on the E291A, E291Q, D284A/E291A, or D284N/E291Q variants of MCP-1 receptor (IC50 exceeding 100,000 nM)[1]. By blocking CCR2 with a concentration of 10 μM, RS102895 reduces the upregulation of extracellular matrix (ECM) protein expression and significantly prevents the expression of fibronectin and type IV collagen proteins in mesangial cells (MCs) stimulated by high glucose (HG) at concentrations of 1 or 10 μM. Furthermore, a 10 μM dose of RS102895 also lowers the enhanced levels of TGF-1 in MCs treated with MCP-1[2].
体内研究
Administered at 3 g/L through intrathecal injection, RS102895 progressively lowers the pain threshold in rats experiencing bone cancer pain (BCP) from day 3 to 9 post-surgery, yet the pain threshold elevates after 12 days. Additionally, it effectively alters the expression patterns of NR2B, nNOS, and SIGIRR in the spinal cord[3].
体外研究
RS102895 hydrochloride acts as a strong antagonist of CCR2, demonstrating an IC50 value of 360 nM, while exhibiting no influence on CCR1. This compound further exerts inhibitory effects on human α1a and α1d receptors, along with the 5HT1a receptor in rat brain cortex cells, showcasing IC50 values of 130, 320, and 470 nM, respectively. It effectively diminishes activity in both the wild type and D284N variant of the MCP-1 receptor, with IC50 figures of 550 nM and 568 nM, respectively, and exhibits a weaker inhibition against the D284A variant of MCP-1 receptor (IC50 of 1892 nM). It displays no impact on the E291A, E291Q, D284A/E291A, or D284N/E291Q variants of MCP-1 receptor (IC50 exceeding 100,000 nM)[1].
By blocking CCR2 with a concentration of 10 μM, RS102895 reduces the upregulation of extracellular matrix (ECM) protein expression and significantly prevents the expression of fibronectin and type IV collagen proteins in mesangial cells (MCs) stimulated by high glucose (HG) at concentrations of 1 or 10 μM. Furthermore, a 10 μM dose of RS102895 also lowers the enhanced levels of TGF-1 in MCs treated with MCP-1[2].
作用机制
RS-102895 hydrochloride prevents MCP-1 from binding to CCR2 by occupying the same binding-site, the inter-helical bundle region on the extracellular side of CCR2 receptor.
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