Table 2.
Antiproliferative potency of NT-7-16 analogs in a panel of cancer cell lines and their microtubule depolymerizing activity in comparison to other pyrroles IC50 ± SD (nM)
| Compound | MDA-MB-435a (nM) | HeLaa (nM) | HeLa WT βIIIa (nM) | Rr | SK-OV-3a (nM) | SK-OV-3 MDR-1/M-6-6a (nM) | Rr | EC50a (nM) | EC50/IC50 | HINT Score |
|---|---|---|---|---|---|---|---|---|---|---|
| NT-7-16c (4a) | 10.4 ± 0.5 | 12.9 ± 0.8 | 15.7 ± 0.2 | 1.2 | 15.2 ± 0.8 | 10.6 ± 0.3 | 0.70 | 37 | 3.6 | 824 |
| NT-9-21c (4b) | 116 ± 4 | 131 ± 8 | 140 ± 20 | 1.1 | 210 ± 70 | 140 ± 8 0 | 0.67 | 1000 | 8.6 | 772 |
| KL-3-95 (9) | 19.6 ± 1.8 | 20.6 ± 1.9 | 26.1 ± 0.8 | 1.3 | 26.2 ± 2.1 | 42.2 ± 5.5 | 1.6 | 88 | 4.5 | 588 |
| NT-7-45 (Z) (12a) | 25.3 ± 3.1 | 29.4 ± 1.0 | 31.3 ± 0.5 | 1.1 | 33.7 ± 1.3 | 49.6 ± 2.4 | 1.5 | 108 | 4.2 | 554 |
| NT-7-45 (E) (12b) | 14.0 ± 0.8 | 18.0 ± 0.9 | 25.0 ± 1.4 | 1.4 | 23.1 ± 0.5 | 41.6 ± 1.9 | 1.8 | 56 | 4 | 687 |
| NT-7-45 (53:47 mix of E and Z) (12) | 2.7 ± 0.2 | 5.0 ± 0.3 | 4.1 ± 1.0 | 0.9 | 5.3 ± 0.2 | 6.6 ± 1.2 | 1.2 | 9.2 | 3.4 | ND |
| Paclitaxel | 2.0 ± 0.2 | 1.5 ± 0.1 | 21.1 ± 1.8 | 14 | 3.0 ± 0.3 | 2330 ± 150 | 776 | ND | ND | ND |
a
IC50 values are the mean of at least 3 independent experiments each conducted in triplicate ± SD.
b
n=3
c
From reference 7.