Anti-tumor effects of an Id antagonist with no acquired resistance
Bibliographic record
Abstract
Summary Id proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. Id proteins inhibit basic HLH transcription factors through protein-protein interactions, often inhibiting differentiation and sustaining proliferation. We recently identified a small-molecule, AGX51, which targets Id proteins for degradation and impairs ocular neovascularization in mouse models. Here we show that AGX51 treatment of cancer cell lines impaired cell growth and viability that results from a dramatic increase in ROS production upon Id degradation. In mouse models, AGX51 treatment suppressed breast cancer colonization in the lung, regressed the growth of paclitaxel-resistant breast tumors when combined with paclitaxel and reduced tumor burden in a model of sporadic colorectal neoplasia. Furthermore, in cells and mice, we failed to observe acquired resistance to AGX51 likely the result of the immutability of the binding pocket and efficient degradation of the Id proteins. Thus, AGX51 is a first-in-class compound that antagonizes Id proteins, shows strong anti-tumor effects and may be further developed for the management of multiple cancers.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".