Entdeckung einer chemischen Sonde für MLLT1/3‐YEATS‐Domänen
Bibliographic record
Abstract
Abstract YEATS‐Domänen(YD)‐enthaltende Proteine sind eine neue Klasse epigenetischer Zielstrukturen für die Wirkstoffentwicklung. Die YD‐enthaltenden Proteine MLLT1 (ENL/YEATS1) und MLLT3 (AF9/MLLT3) sind oft in Krebs dereguliert und wurden daher als potentielle Zielstrukturen für neue Therapieansätze diskutiert. Wir berichten hier die Entwicklung und Charakterisierung des ersten niedermolekularen Inhibitors der YD in MLLT1 und MLLT3, SGC‐iMLLT. Er ist ein potenter und selektiver Inhibitor der MLLT1/3‐Histon‐Interaktion und zeichnet sich durch exzellente Selektivität gegenüber anderen menschlichen YD‐Proteinen (YEATS2/4) und Bromodomänen aus. Aufgrund der zellulären Aktivität eignet sich die entwickelte chemische Sonde um die biologischen Funktionen der YD in MLLT1/3 und das therapeutische Potential dieser kleinen Proteininteraktionsdomänen zu verstehen.
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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) | 0.005 | 0.001 |
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".