Development of SGC-GAK-1 as an orally active in vivo probe for cyclin G associated kinase through cytochrome P450 inhibition
Bibliographic record
Abstract
Abstract SGC-GAK-1 ( 1 ), a potent, selective, cell-active chemical probe for cyclin G associated kinase (GAK), was rapidly metabolized in mouse liver microsomes by P450 mediated oxidation. 1 displayed rapid clearance in mice, limiting its utility for in vivo studies. All chemical modifications of 1 that improved metabolic stability led to a loss in GAK activity. However, pretreatment of liver microsomes with the irreversible cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) decreased intrinsic clearance of 1 . Coadministration of ABT also greatly improved plasma exposure of 1 in mice, supporting its use as a chemical probe to study the in vivo biology of GAK inhibition.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".