Table 2.
In vitro evaluation of the CXCR4 antagonists in the competition binding and signalling experiments.
| Compound | Competition Binding Assay a IC50 (nM) |
Ca2+ Signalling Assay b IC50 (nM) |
|||
|---|---|---|---|---|---|
| 12G5 | CXCL12 | CCL5 | CXCL12 | CCL3L1 | |
| Cu2L1 | 50.1 ± 7.2 | 5.1 ± 0.9 | >1000 | 113 ± 12.7 | >20,000 |
| Zn2L1 | 5.9 ± 2.4 | 0.41 ± 0.03 | >1000 | 4.9 ± 2.9 | >2000 |
| Cu2L2 | 465 ± 155 | 8.9 ± 1.1 | >1000 | 185 ± 75 | >20,000 |
| Zn2L2 | 1.4 ± 0.4 | 0.43 ± 0.00 | 255 ± 58 | 5.6 ± 1.9 | 120 ± 28 |
| Cu2L3 | 1.12 ± 0.15 | 0.54 ± 0.03 | 741 ± 145 | 3.1 ± 0.3 [23] | >1000 |
| Zn2L3 | 1.9 ± 0.3 | 0.90 ± 0.23 | >1000 | 17.5 ± 11.7 | >5000 |
| Cu2L4 | 1.3 ± 0.4 | 0.53 ± 0.03 | 702 ± 219 | 11.9 ± 8.3 | >10,000 |
| Zn2L4 | 3.4 ± 0.2 | 2.1 ± 0.1 | >1000 | 66.1 ± 0.9 | >20,000 |
| Cu2L5 | 1.9 ± 0.6 | 0.83 ± 0.02 | >1000 | 11.3 ± 4.7 | >15,000 |
| Zn2L5 | 8.6 ± 4.7 | 0.49 ± 0.01 | >1000 | 10.3 ± 6.6 | >20,000 |
| AMD3100 | 83.7 ± 8.3 | 18.0 ± 4.2 [37] | >1000 | 203.5 ± 19.4 [23] | >20,000 |
| Maraviroc | - | >1000 | 10.3 ± 3.5 | >20,000 | 3.1 ± 0.6 |
a Concentration required to inhibit the binding of PE-conjugated anti-CXCR4 mAb (12G5) in T-lymphocytes or the binding of AF647-labelled chemokines CXCL12 or CCL5 in PMBCs by 50%. b Concentration required to inhibit chemokine-induced Ca2+ signalling in CXCR4- and CCR5-transfected cells by 50%. Data are presented as the mean ± SEM of two to three experiments.