Multi-Parametric SAR Optimization

Discovery - Chemistry

 

Multi-Parametric SAR Optimization is central to Icagen’s early discovery efforts, enabling faster, more efficient progression toward Lead or Pre-Candidate status. The simultaneous optimization of physicochemical properties, such as potency, solubility, stability, and permeability, not only improves overall efficiency with regard to lead optimization, but also increases the candidate’s probability of success through preclinical and clinical trials.

Icagen’s lead discovery process and capabilities include:

  • SAR Expansion
    • Identifying key moieties responsible for steep changes in SAR activities
    • Identifying main drivers of properties to optimize (potency, selectivity, solubility, ADME)
    • Understanding key property drivers (solubility, HPLC LogD, microsomal stability, passive cell membrane permeability)
    • Re-scaffolding, tuning polarity and predicting in silico properties
  • Lead Optimization
    • Structure-based design (or pharmacophore models) Intellectual property creation and protection
    • Selectivity panels and anti-targets
    • Tuning ADME and phys-chem properties
    • Supporting PK and PD studies

Icagen’s compound optimization methodologies involve:

  • Rapid analoging – parallel synthesis
  • Solution- and/or solid-phase methods
  • Scaffold/reagent sourcing
  • Patent space assessment
  • Predictive in silico models (SAR, ADME, polarity, solvation)
  • Salt selection
  • Scale up to 0.5-3 g
  • Finalization of compounds at Icagen's U.S. facilities