Potent Targeting of the STAT3 Protein in Brain Cancer\nStem Cells: A Promising Route for Treating Glioblastoma
Bibliographic record
Abstract
The <i>STAT3</i> gene is abnormally active in glioblastoma\n(GBM) and is a critically important mediator of tumor growth and therapeutic\nresistance in GBM. Thus, for poorly treated brain cancers such as\ngliomas, astrocytomas, and glioblastomas, which harbor constitutively\nactivated STAT3, a STAT3-targeting therapeutic will be of significant\nimportance. Herein, we report a most potent, small molecule, nonphosphorylated\nSTAT3 inhibitor, <b>31 (SH-4-54)</b> that strongly binds to\nSTAT3 protein (<i>K</i><sub>D</sub> = 300 nM). Inhibitor <b>31</b> potently kills glioblastoma brain cancer stem cells (BTSCs)\nand effectively suppresses STAT3 phosphorylation and its downstream\ntranscriptional targets at low nM concentrations. Moreover, in vivo, <b>31</b> exhibited blood–brain barrier permeability, potently\ncontrolled glioma tumor growth, and inhibited pSTAT3 in vivo. This\nwork, for the first time, demonstrates the power of STAT3 inhibitors\nfor the treatment of BTSCs and validates the therapeutic efficacy\nof a STAT3 inhibitor for GBM clinical application.
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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 | 0.001 |
| 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) | 0.004 | 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".