CRYSTALSFIRST® hit-to-lead services focus on transforming initial hits into optimized lead compounds with drug-like properties. We leverage structure-based drug design, iteratively refining hits using crystallography insights and medicinal chemistry expertise. Our platform enables rapid cycles of design-test-optimize: fragment hits discovered via SmartSoak® are elaborated with guidance from FragAI generative models and medicinal chemists. This closed-loop process yields improved analogs which we validate through co-crystal structures and biophysical assays, ensuring each design cycle enhances potency, selectivity, and ADME properties. Working in tandem with medicinal chemistry, CrystalsFirst drives lead optimization with a data-driven mindset. We often advance multiple chemotypes in parallel, de-risking development by exploring diverse binding pockets and modes of action.
Our approach shortens the hit-to-lead timeline compared to conventional methods. The outcome is well-characterized lead series with demonstrated efficacy and clear next-step chemistry plans – ready to progress toward preclinical development.
