Pre-Conference Day

Identifying RNA targets that are both biologically meaningful and chemically tractable

remains one of the biggest bottlenecks in RNA-targeted drug discovery. Many RNA

regions are capable of binding small molecules, but only a subset controls diseaserelevant

biology in a way that can support a therapeutic hypothesis.

Join RNA biologists, screening scientists, translational researchers, and discovery

teams to explore practical strategies for:

• Identifying which RNA transcripts, structures and regulatory elements are suitable for small-molecule intervention
• Moving beyond one-at-a-time target discovery with scalable screening and functional assay approaches
• Using chemical probing to distinguish dynamic RNA structures from functionally important conformational switches
• Matching each RNA target to the most appropriate therapeutic hypothesis, from splice modulation to direct binding, degradation or translational inhibition
• Learning from screening approaches that failed to generate actionable targets, functional hits or reliable discovery decisions

A major challenge in RNA-targeted drug discovery is determining where small

molecules bind on RNA, what structures they recognize, and whether those binding

events translate into functional outcomes. As structural, probing, and biophysical tools

advance, the field still lacks standardized approaches for connecting RNA structure,

binding-site identification, and compound optimization.

Join medicinal chemists, structural biologists, RNA biologists, and teams improving

structure-guided design to explore practical strategies for:

• Predicting RNA ligandability by identifying structures that can support selective small-molecule binding
• Prioritizing tractable RNA targets by linking function, binding pockets and confidence in on-target engagement
• Evaluating biophysical and structural methods to measure RNA ligand recognition, affinity and conformational change

The chemical space explored for RNA-targeted small molecules remains relatively

narrow and heavily influenced by existing patents, public datasets, and legacy screening

collections. While these efforts have produced important advances, they have also

concentrated discovery around a limited set of chemical frameworks and design

principles. As more organizations pursue splicing modulation, RNA degradation,

translational control, and direct RNA binding, there is growing interest in identifying

chemical matter that extends beyond familiar RNA-targeted chemotypes while

remaining productive, interpretable, and actionable for discovery.

This workshop will bring together medicinal chemists, computational chemists,

screening scientists, chemical biologists, and RNA drug discovery leaders to discuss

how the field can broaden RNA-focused chemical space.

Topics for discussion include:

• Examining where current RNA-targeted chemistry is concentrated across patents, public datasets, commercial libraries, and internal collections
• Exploring how chemically diverse yet information-rich chemical spaces can improve both hit discovery and the extraction of actionable design principles
• Comparing chemical requirements across splicing modulation, RNA degradation, translational inhibition, and direct RNA binding
• Discussing how molecular glue degrader thinking could inspire new approaches to RNA or protein depletion
• Evaluating how public structures, shape-based searching, cheminformatics, and AI can support broader chemical exploration