Development of a high-throughput assay to identify inhibitors of the ubiquitin-conjugating enzyme UBCH10
Bibliographic record
Abstract
UBCH10 is an ubiquitin-conjugating enzyme (E2) of the anaphase-promoting complex E3 ligase, a key regulator of the cell cycle. The UBCH10 gene and protein are frequently upregulated in multiple solid tumors, associated with an unfavorable outcome. Accumulating evidence from studies of human cancer cell lines, mouse transgenic models, and analyses of clinical samples suggest that UBCH10 is a potential cancer drug target. No small molecule inhibitor of UBCH10 has been reported in the literature. Here, we described the development and optimization of a novel time-resolved fluorescence resonance energy transfer (TR-FRET) UBCH10 assay based on the self-polyubiquitination of the enzyme in the absence of E3. The homogenous assay is robust, sensitive, and scalable to different multi-well formats for high-throughput screening (HTS). We demonstrate the suitability of the TR-FRET assay to identify chemical inhibitors of UBCH10 in a pilot HTS campaign.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".