Scope library: a chemical space between fragments and full molecules for tractable hits
- Scope defines a chemical space between fragments and elaborated low-molecular-weight library compounds, emphasizing compound quality, ligand efficiency and selected property ranges to keep hits tractable for medicinal chemistry.
- Scope ring systems (ring-X-ring) organize the space and guide intentional functionalization toward low- to mid-micromolar potency; a roughly 10k-compound set suits medium-throughput SPR, native MS, DSF and biochemical screens.
- Case studies on trypanosomal CLK1, a 14-3-3/ERα molecular glue project and SARS-CoV-2 Mpro show comparable primary hit rates to diversity sets, with better ligand efficiency after counter-screening.
💡 Points
Honestly, the pitch I like here is hits you can actually start working on: a library sitting between fragments and full-size compounds, built around ligand efficiency, with ring-X-ring cores that tell you where to functionalize next. A 10k set fits SPR, native MS and DSF, so a smaller group can run it. The open question is whether primary hit rates on par with diversity sets, with better LE after counter-screening, hold up beyond three targets, and how much the scaffold constraint narrows novelty.