Lead Optimization

If you already have a lead, and are looking to advance that to a clinical candidate, we can help. If you’re in the early stages of lead-optimization, where potency improvement is the main goal, we offer the full range of structure-based design approaches: See Computational Technologies.

At later stages, the roadblocks to optimization are typically not potency, but off-target effects or PK properties. We can develop proprietary models based on your data for those off-target effects, to help you design out those off-target effects while maintaining potency.

Past successful collaborations have included:

  • Working as a full-fledged project team member, using structure-based design in an iterative design phase, advanced a molecule into pre-clinical studies
  • Developed CYP models to help a client understand the challenges they faced in creating an analog in their series free of CYP issues
  • Built structural models for an existing series that had inexplicably favorable selectivity, to help the chemists design analogs which improved the potency while maintaining the selectivity. (These models were later confirmed experimentally in the literature).
  • Built a homology model for a novel protein with no known Xray structure, and used this to both rationalize a client’s existing SAR and to provide design ideas for future analogs

"One molecule does not disprove a hypothesis."
—Jackson B. Hester

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