ZK 756326 is a selective, non-peptide CCR8 chemokine receptor agonist (IC50: 1.8 μM, in human; 2.6 μM, in mouse). Displays no activity at CCR4/5 and CXCR3/4 and shows higher 28-fold selectivity over 26 other GPCRs (less selective at α2A and 5-HT receptors). Induces chemotaxis and inhibits Env-mediated (HIV) cell-cell fusion.

CCR8(mouse):2.6 μM, CCR8(human):1.8 μM

ZK 756326在表达人CCR8的细胞中刺激细胞外酸化，这一效应是受体特异性的，且通过Gαi介导，因为可以通过用百日咳毒素处理来阻断。与CCL1相似，ZK 756326抑制了表达CD4和CCR8的细胞的人类免疫缺陷病毒(HIV)融合。但不同于mCCL1，ZK 756326能结合到并激活一种经过突变以在酪氨酸14和15位点去除O-连带硫酸化的mCCR8形式。因此，ZK 756326很可能不以与CCL1相同的方式结合，但能激活转导信号事件中涉及的开关机制[1]。

Cells are resuspended in RPMI with 1% (w/v) BSA and 25 mM HEPES, pH 7.4 (3 × 105 cells/well), and 100-μl aliquots were loaded into upper inserts. Samples of mCCL1 and ZK 756326 prepared in 600 μl of the same medium were placed in the lower wells. After incubation (2 h at 37°C), inserts were removed, and the migrated cells were counted in an EPICS XL flow cytometer. Duplicate wells were used for each point. A migration index was established as the ratio of the number of cells that had migrated in response to the chemokine or to ZK 756326 divided by the number of cells that had migrated in response to buffer alone. (Only for Reference)