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
- 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
- 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.