Structure‐Based Virtual Screening and Electrophysiological Evaluation of New Chemotypes of K<sub>v</sub>1.5 Channel Blockers
Bibliographic record
Abstract
Atrial fibrillation (AF) is the most prevalent nonfatal cardiac rhythm disorder associated with an increased risk of heart failure and stroke. Considering the ventricular side effects induced by anti-arrhythmic agents in current use, K(v)1.5 channel blockers have attracted a great deal of deliberation owing to their selective actions on atrial electrophysiology. Herein we report new chemotypes of K(v)1.5 channel blockers that were identified through a combination of structure-based virtual screening and in silico druglike property prediction including six scoring functions, as well as electrophysiological evaluation. Among them, five of the 18 compounds exhibited >50 % blockade ratio at 10 microM, and have structural features different from conventional K(v)1.5 channel blockers. These novel scaffolds could serve as hits for further optimization and SAR studies for the discovery of selective agents to treat AF.
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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".