Table 5.
Cell-based activity of representative analogs.
| A673 cells | MiaPaCa-2 cells | |||||
|---|---|---|---|---|---|---|
|
|
||||||
| Analog | Lactate inh. | Cytotoxicity | Long-term growth inh. | Lactate inh. | Cytotoxicity | Long-term growth inh. |
| IC50 ± SD (μM) a | IC50 ± SD (μM) a | IC50 (μM)c | IC50 ± SD (μM) a | IC50 ± SD (μM) a | IC50 (μM) c | |
| 1 | >57 | >57 | >20 | >57 | >57 | >20 |
| 2 | 14.5 ± 5.7 | >57 | 0.84 | 12.6 ± 3.6 | 28.4 ± 11.2b | 1.37 |
| 3 | 1.44 ± 0.09 | 2.63 ± 0.3 | - | 0.877 ± 0.059 | 1.24 ± 0.08 | - |
| 33 | >57 | >57 | - | >57 | >57 | - |
| 36 | >57 | >57 | - | >57 | >57 | - |
| 37 | 26.8 ± 3.1 | >57 | - | 27.7 ± 1.9 b | >57 | - |
| 38 | 30.0 ± 3.5b | >57 | - | 29.9 ± 0.1b | >57 | - |
| 42 | 30.8 ± 2.1b | >57 | - | >57 | >57 | - |
| 43 | 25.2 ± 19.4b | >57 | - | 33.5 ± 0.1b | >57 | - |
| 44 | 15.2 ± 3.2 | >57 | >20 | 9.88 ± 1.26 | >57 | >20 |
| 46 | 19.9 ± 4.5 | >57 | - | 7.24 ± 0.47 | >57 | - |
| 47 | 26.8 ± 3.1 | >57 | - | 22.4 ± 1.8 | >57 | - |
| 54 | 16.5 ± 6.2 | >57 | - | 26.6 ± 0.1b | >57 | - |
| 55 | >57 | >57 | - | >57 | >57 | - |
| 56 | 9.45 ± 0.01 | >57 | - | 17.7 ± 6.6 | >57 | - |
| 57 | 4.35 ± 1.21 | >57 | >20 | 4.80 ± 2.47 | >57 | >20 |
| 58 | 14.7 ± 3.6 | >57 | - | 17.5 ± 1.2 | >57 | - |
| 60 | 1.92 ± 0.43 | 25.8 ± 3.0 | - | 1.96 ± 0.13 | 28.3 ± 7.1 | - |
| 61 | 0.983 ± 0.335 | 13.9 ± 0.9 | 21.09 | 1.34 ± 0.15 | 18.9 ± 1.3 | 8.00 |
| 62 | 3.37 ± 0.39 | 24.8 ± 1.6 | >20 | 5.12 ± 0.33 | 24.9 ± 1.6 | >20 |
| 63 | 0.517 ± 0.088 | 2.90 ± 0.3 | 2.23 | 0.854 ± 0.059 | 3.96 ± 0.68 | 1.21 |
a
IC50 values represent the half maximal (50%) inhibitory concentration as determined in the HTS assay (n = 3).
b
Max. response was less than 50% and thus IC50 values should be considered as lower confidence.
c
IC50 values represent average of 2 assay replicates