Investigation of the mechanism of action of a potent pateamine A analog, des-methyl, des-amino pateamine A (DMDAPatA)
Bibliographic record
Abstract
The natural product pateamineA (PatA) is a highly potent antiproliferative agent. PatA and the simplified analog desmethyl, desamino pateamineA (DMDAPatA) have exhibited cytotoxicity selective for rapidly proliferating cells, and have been shown to inhibit cap-dependent translation initiation through binding to eIF4A (eukaryotic initiation factor 4A) of the eIF4F complex. PatA and DMDAPatA are both known to stimulate the RNA-dependent ATPase, and ATP-dependent RNA helicase activities of eIF4A. The impact of other eIF4F components, eIF4E and eIF4G, on DMDAPatA action were investigated in vitro and in cultured mammalian cells. The perturbation of the eIF4A-eIF4G association was found to be eIF4E- and mRNA cap-dependent. An inhibitory effect on helicase activity of eIF4A was observed when it was part of a complex that mimicked the eIF4F complex. We propose a model of action for DMDAPatA (and by supposition PatA) where the cellular activity of the compound is dependent on an "active" eIF4F complex.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".