Discovery of RNA‐Targeting Small Molecules: Challenges and Future Directions
Bibliographic record
Abstract
RNA-targeting small molecules represent a transformative frontier in drug discovery, offering novel therapeutic avenues for diseases traditionally deemed undruggable. This review explores the latest advancements in the development of RNA-binding small molecules, focusing on the current obstacles and promising avenues for future research. We highlight innovations in RNA structure determination, including X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy, which provide the foundation for rational drug design. The role of computational approaches, such as deep learning and molecular docking, is emphasized for enhancing RNA structure prediction and ligand screening efficiency. Additionally, we discuss the utility of focused libraries, DNA-encoded libraries, and small-molecule microarrays in identifying bioactive ligands, alongside the potential of fragment-based drug discovery for exploring chemical space. Emerging strategies, such as RNA degraders and modulators of RNA-protein interactions, are reviewed for their therapeutic promise. Specifically, we underscore the pivotal role of artificial intelligence and machine learning in accelerating discovery and optimizing RNA-targeted therapeutics. By synthesizing these advancements, this review aims to inspire further research and collaboration, unlocking the full potential of RNA-targeting small molecules to revolutionize treatment paradigms for a wide range of diseases.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".