Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
Bibliographic record
Abstract
Cancer stem cells (CSCs) are documented to play a key role in tumorigenesis and therapy resistance. Despite significant progress in clinical oncology, CSC reservoirs remain elusive and difficult to eliminate. Reverse-turn peptidomimetics were characterized as disruptors of CBP/beta-Catenin interactions and represent a promising avenue to curb hyperactive canonical Wnt/beta-Catenin signaling in CSCs. Recent studies suggested Sam68 as a critical mediator of reverse-turn peptidomimetics response in CSC populations. Using computational and biochemical approaches we confirmed Sam68 as a primary target of reverse-turn peptidomimetics. Furthermore, we executed an in silico drug discovery pipeline to identify yet uncharacterized reverse-turn peptidomimetic structures displaying superior anti-CSC activity in transformed pluripotent and colorectal cancer cell models. Thus, we identified YB-0158 as a reverse-turn peptidomimetic small molecule with enhanced translational potential, altering key hallmarks of human colorectal CSCs in patient-derived ex vivo organoids and in vivo serial tumor transplantation.
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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 | 0.001 |
| 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".