SNX-2112 in vitro activity for Hsp90 clients
| Hsp90 client assays . | IC50, nM . | |
|---|---|---|
| SNX-2112 . | 17-AAG . | |
| p-ERK degradation (A375: melanoma) | 48 ± 8 | 434 ± 196 |
| p-ERK degradation (AU565: breast) | 10 ± 6 | 22 ± 6 |
| EphA2 degradation (A375) | 133 ± 22 | 367 ± 49 |
| Her2 degradation (SKBR3: breast) | 6 ± 0.5 | 0.4 ± 0.3 |
| Her2 degradation (AU565) | 10 ± 0.8 | 4 ± 1 |
| p-S6 degradation (A375) | 4 ± 0.2 | 308 ± 32 |
| AKT degradation (A375) | 163 ± 27 | 189 ± 53 |
| p-AKT degradation (A375-IGF-1) | 70 ± 15 | 120 ± 32 |
| NF-κB translocation (HUVEC-IL-1β) | 175 ± 33 | 539 ± 124 |
| B-Raf degradation (A375) | 319 ± 63 | 315 ± 74 |
| p-c-JUN (HUVEC-IL-1β) | 327 ± 84 | 623 ± 143 |
| AKT degradation (NCI-H929: myeloma) | 39 ± 0.6 | 684 ± 141 |
| p-STAT3 degradation (NCI-H929) | 41 ± 0.8 | 920 ± 10 |
| p-ERK degradation (NCI-H929) | 30 ± 1 | 813 ± 17 |
| p-MEK degradation (NCI-H929) | 40 ± 0.1 | 897 ± 66 |
| Hsp90 client assays . | IC50, nM . | |
|---|---|---|
| SNX-2112 . | 17-AAG . | |
| p-ERK degradation (A375: melanoma) | 48 ± 8 | 434 ± 196 |
| p-ERK degradation (AU565: breast) | 10 ± 6 | 22 ± 6 |
| EphA2 degradation (A375) | 133 ± 22 | 367 ± 49 |
| Her2 degradation (SKBR3: breast) | 6 ± 0.5 | 0.4 ± 0.3 |
| Her2 degradation (AU565) | 10 ± 0.8 | 4 ± 1 |
| p-S6 degradation (A375) | 4 ± 0.2 | 308 ± 32 |
| AKT degradation (A375) | 163 ± 27 | 189 ± 53 |
| p-AKT degradation (A375-IGF-1) | 70 ± 15 | 120 ± 32 |
| NF-κB translocation (HUVEC-IL-1β) | 175 ± 33 | 539 ± 124 |
| B-Raf degradation (A375) | 319 ± 63 | 315 ± 74 |
| p-c-JUN (HUVEC-IL-1β) | 327 ± 84 | 623 ± 143 |
| AKT degradation (NCI-H929: myeloma) | 39 ± 0.6 | 684 ± 141 |
| p-STAT3 degradation (NCI-H929) | 41 ± 0.8 | 920 ± 10 |
| p-ERK degradation (NCI-H929) | 30 ± 1 | 813 ± 17 |
| p-MEK degradation (NCI-H929) | 40 ± 0.1 | 897 ± 66 |
Cells were cultured with SNX-2112 or 17-AAG for 48 hours, and in vitro activity of SNX-2112 against various hsp90 clients was evaluated by high content cell imaging assay. IC50 values shown are means plus or minus SD of triplicate determinations.