Combinatorial Targeting of Common Docking and ATP Binding Sites on Mps1 MAPK for Management of Pathogenic Fungi
Why this work is in the frame
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Bibliographic record
Abstract
, the pathogen of rice blast disease, has been shown to be a molecular target for fungicide research. Here, we present compound TAK-733 that interacts with the common docking (CD) site of Mps1 and can be used in combination with ATP-competitive inhibitors. We initially identified compounds PLX-4720 and TAK-733 that interact with Mps1. Subsequent assays show that PLX-4720 is an ATP-competitive inhibitor, whereas TAK-733 binds to the CD site of Mps1─an interaction site for its MAPKK─but not to the ATP-binding pocket as it does in the kinase MEK1. In vivo assays demonstrated that TAK-733 exhibits combinational effects with ATP-competitive inhibitors PLX-4720 and A378-0. Collectively, we present TAK-733 as having a new mechanism of action suitable for combinational application with ATP-competitive inhibitors in the management of pathogenic fungi.
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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 | 0.000 |
| 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) | 0.000 | 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 it