ZK 756326 is a non-peptide agonist of the CC chemokine receptor CCR8. It inhibits binding of CCL1 to human CCR8 (IC50 = 1.8 μM) and induces Gai-mediated calcium-mobilization in U87 cells expressing the receptor.1 It exhibits greater than 28-fold selectivity for CCR8 over 26 other GPCRs but also binds to the serotonin (5-HT) receptor subtypes 5-HT1A, 5-HT2B, 5-HT2C, and 5-HT5A with IC50 values of 5.4, 4.4, 34.8, and 16 μM, respectively. ZK 756326 stimulates extracellular acidification in cells expressing human and mouse CCR8 (EC50s = 254 nM and 2.6 μM, respectively). ZK 756326 induces ERK phosphorylation, exhibits leukocyte chemotactic activity, and inhibits HIV fusion of cells expressing CD4 and CCR8.
|1. Haskell, C.A., Horuk, R., Liang, M., et al. Identification and characterization of a potent, selective nonpeptide agonist of the CC chemokine receptor CCR8. Mol. Pharmacol. 69(1), 309-316 (2005).