Fragment-to-Lead Medicinal Chemistry Publications in 2024: A Tenth Annual Perspective
Bibliographic record
Abstract
Fragment-based drug discovery (FBDD) has led to dozens of clinical compounds, including eight approved drugs. For the past decade, we have published an annual review of successful fragment-to-lead (F2L) medicinal chemistry programs. This Perspective marks the tenth in the series. We analyze the 18 F2L case studies from 2024 and put them in the context of the larger set of 233 examples dating back to 2015. We hope that the lessons herein will both inform and inspire researchers to discover the next generation of drugs.
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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 | 0.008 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.010 | 0.010 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.031 | 0.010 |
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".