Table 3. Performance of 15 hits and erbstatin analog against a panel of kinases.
Summary assessment of the 16 hits and the erbstatin analog effects on the in-vitro enzymatic activities of EGFR, SRC, ABL, and VEGF1 kinases on the panel. The reported IC50 values ±standard deviation were calculated based on dose response studies for each confirmed hit using the luminescence ADP kinase Glo assay as described under Materials and Methods.
| Luminescence ADP kinase assay IC50 (μM) | ||||||
|---|---|---|---|---|---|---|
| Compound name | Molecular target | EGFR | SRC | ABL | VEGFR1 | |
| Known EGFR inhibitors | BIBU 1361 | EGFR kinase | < 0.01 | > 10 | > 10 | > 10 |
| Tyrphostin AG 1478 | EGFR kinase | < 0.01 | 2.6±1.3* | 2.0±0.6* | > 10* | |
| PD 153035 | EGFR kinase | < 0.01 | > 10 | 1.8±0.3* | > 10 | |
| Erlotinib | EGFR kinase | < 0.01 | 2.4±0.7* | 2.4±0.6* | 1.3±0.1* | |
| Gefitinib | EGFR kinase | < 0.01 | > 10 | > 10 | > 10 | |
| Lapatinib | EGFR kinase | 0.54±0.02 | > 10 | > 10 | > 10 | |
| GW 2974 | EGFR kinase | 0.12±0.03 | > 10 | > 10 | > 10 | |
| GW 583340 | EGFR kinase | 1.3±0.1 | > 10 | > 10 | > 10 | |
| Erbstatin analog | EGFR kinase | > 10 | > 10 | > 10 | > 10 | |
| Other confirmed granule formation inhibitors | ZM-306416 | VEGFR kinase | < 0.01 | 0.33±0.08 | 1.3±0.2* | 0.33±0.04 |
| Camptothecin | Topoisomerase I | > 10 | > 10 | > 10 | > 10 | |
| PKC 412 | Pan-kinase inhibitor | > 10* | > 10 | > 10 | > 10 | |
| Aminopurvalanol A | CDKs | > 10* | 0.12±0.02 | 1.5±0.5 | > 10 | |
| Confirmed granule formation activators | Flurandrenolide | Corticosteroid | > 10 | > 10 | > 10 | > 10 |
| Beclomethasone | Corticosteroid | > 10 | > 10 | > 10 | > 10 | |
| Ebastine | H1 receptor | > 10 | > 10 | > 10 | > 10 | |
*
partial inhibition: a clear upper asymptote was not reached at the highest concentrations tested, or the upper asymptote did not reach 100% inhibition.