SU1498 is a direct inhibitor of ERK and sensitizes breast cancer cells to stress‐induced apoptosis
Bibliographic record
Abstract
SU1498, an inhibitor of vascular endothelial growth factor receptor‐2 (VEGFR‐2) has been used to study receptor function. In addition to its anti‐VEGFR‐2 activity, SU1498 was found to stimulate the accumulation of phosphorylated extracellular signal‐regulated protein kinases (ERKs), generally an indication of ERK activation, in human umbilical vein endothelial cells. The enhanced accumulation of phospho‐ERKs is observed only in stimulated cells, SU1498 by itself is ineffective. Activation of the classical MAP kinase signalling pathway was required to generate phospho‐ERK. However, SU1498 also blocked the kinase activity of phospho‐ERK, both in a direct assay and in cells treated with the compound. Therefore, there was an apparent contradiction, an ERK inhibitor that results in the hyperphosphorylation of ERK. SU1498 prevents dephosphorylation of phospho‐ERK by MAP kinase phosphatase‐1, without directly affecting the phosphatase activity, suggesting that SU1498 associates with phospho‐ERK, inhibiting kinase activity, but also making the kinase inaccessible to ERK‐specific phosphatases. In breast cancer cells, SU1498 inhibits proliferation and sensitizes the cells to stress‐induced apoptosis. As resistance to apoptosis and enhanced proliferation are both characteristics of cancer cells, these studies suggest a novel way in which MAP kinase signaling pathway may be blocked in human cancers. Supported by a NSERC grant to ATK
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".