STAT Protein Thermal Shift Assays to Monitor Protein‐Inhibitor Interactions
Bibliographic record
Abstract
STAT3 protein is a sought-after drug target as it plays a key role in the progression of cancer. Many STAT3 inhibitors (STAT3i) have been reported, but accumulating evidence suggests many of these act as off-target/indirect inhibitors of STAT signaling. Herein, we describe the STAT protein thermal shift assay (PTSA) as a novel target engagement tool, which we used to test the binding of known STAT3i to STAT3 and STAT1. This revealed STATTIC, BP-1-102, and Cpd188 destabilized both STATs and produced unique migratory patterns on SDS-PAGE gels, suggesting covalent protein modifications. Mass spectrometry experiments confirmed that these compounds are nonspecifically alkylating STATs, as well as an unrelated protein, NUDT5. These experiments have highlighted the benefits of PTSA to investigate interactions with STAT proteins and have helped reveal the novel reactivity of Cpd188. The described PTSA represents a promising chemical biology tool that could be applied to an array of other protein targets.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".