Why Fragment Screening?

In recent years fragment screening has been widely adopted for hit generation by the pharmaceutical industry as a complementary approach to High Throughput Screening (HTS).

Instead of drug-like compounds (MW >400) chemical fragments (MW <300) are screened that exhibit much weaker binding interactions with the target but are more likely to fit into a binding pocket. This results in a higher hit rate and in hits that leave room for chemical expansion to evolve into promising leads.

Fragment Screening versus HTS

Fragment Screening

  • Lower cost
  • Small compound libraries
  • MW <300, simpler structures
  • “Rule of 3”
  • Need to detect activities ≤ mM
  • High concentration screens
  • Biophysical & binding assays
  • High hit rate (8-10%)
  • Proven success
  • Better coverage of chemical space

HTS

  • Large compound libraries
  • High cost
  • MW >400, complex structures
  • “Rule of 5”
  • Typical activity cut-off ≈ 10 μM
  • Low concentration screens
  • Cellular/biochemical/binding assays
  • Low hit rate (≤ 1%)
  • Proven successes

Fragment screening provides an alternative for lead generation with a lower entry barrier than HTS.

Please contact us for further information. We will be pleased to arrange a teleconference or meeting with our technical experts.