Fragment-based lead generation

- Efficient generation of high-quality starting points

Benefits

Diverse components of chemical space able to interact successfully with a particular binding site can be efficiently identified through screening of well-designed fragment libraries with only a few thousand members. Moreover, fragment-based methods tend to generate more efficient starting points for lead generation than traditional HTS-based methods. This is important since retrospective analyses have shown that ligand efficiency tends to decrease during lead generation and optimization of compound series. The weak interactions of fragments with proteins demand sensitive detection systems. High sensitivity combined with low protein consumption and flexible experimental design therefore makes SPR biosensor-based interaction analysis ideal for fragment screening.

Deliverables


  • High-quality fragment leads amenable for rapid and efficient lead generation
  • Initial SAR around the fragment hits

Technical Details

Fragment screening at Beactica is based on the efficient use of SPR biosensor-based techniques. Beactica’s proprietary algorithms for fragment ranking enable superior prioritization of hits. Clients may chose from screening Beactica´s proprietary 2000-member fragment library, or screening of their own libraries.

Beactica_CapabilityNote_103_101006_150dpi

Examples of initial single-concentration fragment screening data for PKA with the detection limit indicated by a red line (top). Dose-response curves are shown for two selected hits (bottom). Experimental data points (red) are theoretically described by a modified Langmuir isotherm that distinguishes a primary interaction from secondary interactions or non-specific signals.

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