Deconstruction of HTS Hits Into Fragments As A Route To Discover Potent BCL6 Inhibitors & Degraders
Time: 2:30 pm
day: Day 1
Details:
- A comprehensive hit id campaign including VS, HTS and FBS combined with integrated orthogonal biophysical approaches (TSA, SPR, LO-NMR) was crucial in the validation of initial BCL6 screening hits
- Deconstruction of the initial HTS hits into smaller fragments improved solubility and facilitated the structure-based drug design to increase potency
- Biophysical validation using orthogonal techniques enabled a high success rate in the determination of protein-ligand crystal structures supporting the discovery of potent BCL6 inhibitors and degraders with anti-proliferative activity in BCL6-dependent cancer cell lines
