A Nucleoside Analogue Bearing a C2′-Stereogenic All-Carbon Quaternary Center for the Treatment of Heart Failure
Bibliographic record
Abstract
Abstract Heart failure (HF) is a significant global health burden with a high mortality rate and no curative or preventative treatment. Many factors can contribute to HF development, including hemodynamic factors and chemotherapy-induced cardiotoxicity. Loss of cardiomyocytes triggers cardiac remodeling and HF, suggesting that strategies aimed at preserving cardiomyocyte survival could provide therapeutic benefits. Here, we describe the biological activity of an adenosine-like nucleoside analogue bearing an all-carbon stereogenic quaternary center that induces a conformational bias to enhance both activity and selectivity. The lead compound, LCB-2122, prevents cardiomyocyte death both in vitro and in vivo in an animal model of acute chemotherapy-induced HF. This protective effect against chemotherapy-induced cardiomyocyte loss is linked to AMPK activation and is abrogated by siRNA-mediated reduction of AMPK expression. The results suggest that targeting cardiomyocyte survival with conformationally biased nucleoside analogues may offer a promising avenue for preventing cardiac dysfunction and the progression of HF.
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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".