Chemical Library

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xFOREST RNA-focused Compound Library

Both screening technologies are a multiplication, and the compound library is one of its two terms. Ours is a focused library: more than 60,000 compounds chosen because structured RNA is what they have to bind, drawn from a collection of over 170,000. What makes it ours is not its size. It is that every generation was selected on the results of the one before it.

The library selection loop Upper register: three stations in a loop - a compound library drawn as a stack of bars, a screen drawn as a small matrix with one gold hit cell, and a selection step drawn as a hexagon - joined left to right by turquoise arrows and closed by a return arrow that runs back to the library, annotated as the next generation, repeated. Lower register: a long row of small chemistry marks in which a few are picked out in gold, labelled as the substructure and scaffold classes that turned out to be enriched among binders. Those are what the loop carries back into the next library. LIBRARY SCREEN SELECTION NEXT GENERATION  ×n WHAT COMES BACK CLASSES ENRICHED IN HITS TO THE NEXT LIBRARY
Schematic of the selection loop. Station glyphs, mark positions and counts are illustrative, not measured data.
INPUT
Commercial chemical space, plus the hit and non-hit record of every screen we have run
OUTPUT
The compound library that both screening technologies multiply against
ROLE
Raising the odds that a well contains a compound structured RNA can read
EFFECT
Higher hit rates against RNA structures, and higher affinity and selectivity of hit compounds
FOCUSED FOR RNA60,000+
TOTAL COLLECTION170,000+
SELECTION CYCLES4
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Four generations, one rising hit rate

The first generation was a diversity collection: broad, unopinionated, and the baseline everything since is measured against. Every generation after it was assembled from what the previous screen had already told us - and each has come back with a higher hit rate than the one before. That trend, not the catalogue, is the asset.

Hit rate across four library generations Four bars rising left to right on a shared baseline. The first and shortest is turquoise and marked as the diversity generation; a dashed line carries its height across the whole chart as the baseline for comparison. The three taller bars are gold; a bracket above them records that together they account for more than 60,000 compounds selected for RNA. Each generation is named and described in the list below the chart. The vertical axis is relative and carries no numbers. HIT RATE · RELATIVE 60,000+ FOR RNA DIVERSITY BASELINE G1 G2 G3 G4
Schematic of the trend across four library generations. Bar heights show the direction of change only - the vertical axis is relative and deliberately unscaled, and the values are not measured data.