Table 1.
Data from dose–response experiments using the luciferase renaturation assay, circular dichroism spectroscopy experiments, a cell-based Hsp90 inhibition assay, and cytotoxicity measurements using a human epithelial cell line
| Peptide | Luciferase renaturation IC50a (μM) |
CD spectroscopy % helicityb |
MDA-kb2 cell culture |
|
|---|---|---|---|---|
| IC50c (μM) | LC50d (μM) | |||
| Novobiocin | 414 ± 28 | 231 ± 42 | 690±188 | |
| Coumermycin A1 |
28.1 ± 2.5 | 15.3 ± 4.1 | 19.1 ± 9.1 | |
| Geldanamycin | 0.282 ± 0.058 | <0.01e | >2f | |
| (2) | 233 ± 9.2 | 20 ± 1 | >160f | >160f |
| (7) | 94.5 ± 3.6 | 43 ± 8 | 18.6 ± 0.3 | 22.9 ± 3.4 |
| (9) | 37.9 ± 4.0 | 64 ± 4 | 18.8 ± 4.5 | 26.6 ± 4.4 |
| (10) | 14.4 ± 2.0 | 50 ± 3 | 15.8 ± 4.3 | 19.1 ± 2.0 |
| (11) | 168 ± 9.0 | 11 ± 1 | >120 | >120 |
| (12) | 137 ± 19 | 29 ± 4 | >67f | >67f |
| (13) | 37.0 ± 3.1 | 37 ± 4 | 121 ± 14 | 97 ± 20 |
| (14) | 38.0 ± 2.2 | 31 ± 5 | 10.4 ± 1.2 | 10.6 ± 3.4 |
| (15) | 32.0 ± 5.7 | 58 ± 4 | 16.8 ± 1.5 | 18.9 ± 1.7 |
| (16) | 8.43 ± 0.09 | 80 ± 2 | >27f | >27f |
| (17) | 4.11 ± 0.19 | 90 ± 2 | 0.73 ± 0.06 | 1.86 ± 0.11 |
From luciferase renaturation assay. IC50 values are ± standard deviation from three independent trials, each performed in triplicate. Values observed for novo-biocin, coumermycin A1, and geldanamycin are in accordance with previously reported values.15
Percent helicity as measured by circular dichroism at 222 nm using 100 μM peptide in 10 mM phosphate buffer at 23 °C.
Dose-dependent inhibition of glucocorticoid-receptor-dependent luciferase expression.
Concentration at which cell viability was reduced by 50% as determined using Promega Cell Titer Glo kit.
Complete suppression of luciferase activity at lowest concentration tested.
No effect observed at the compound’s solubility limit in cell culture media. While all compounds were soluble to 100 μM in phosphate buffer, some compounds had lower solubility limits in cell culture media.