Development of a succinyl CoA:3-ketoacid CoA transferase inhibitor selective for peripheral tissues that improves glycemia in obesity
Bibliographic record
Abstract
studies identified that the antipsychotic diphenylbutylpiperidines can inhibit SCOT and alleviate obesity-related hyperglycemia. Because ketones are a major brain fuel, whereas the diphenylbutylpiperidines have central nervous system-related adverse effects, we aimed to develop a peripheral selective SCOT inhibitor (PSSI). Using a pharmacophore derived from the diphenylbutylpiperidine-SCOT interaction, we synthesized PSSI-51, which inhibited SCOT activity in peripheral but not brain tissue, while decreasing myocardial ketone oxidation. Importantly, PSSI-51 treatment improved glycemia in obese mice and demonstrated reduced brain accumulation compared to the diphenylbutylpiperidine pimozide. We propose that PSSI-51 can lay the foundation for optimizing a new class of brain-impermeable SCOT inhibitors for treating T2D.
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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 | 0.000 | 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 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".