Discovery of RNA‐Targeting Small Molecules: Challenges and Future Directions
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 it