Fragment-based reality check

Researchers at the Burnham Institute for Medical Research have described a drug discovery technique that combines fragment-based synthetic methods and virtual screening to identify inhibitors of protein-protein interactions faster and more efficiently than either method alone.¹ In a proof-of-principle study in human breast cancer cells, reported in the Journal of Medicinal Chemistry, the team identified a selective, low-micromolar inhibitor of X-linked inhibitor of apoptosis.

Team leader Maurizio Pellecchia, professor of infectious diseases at Burnham, told SciBX that an essential feature of the approach is using NMR to confirm the binding behavior of hits. He said this is particularly useful in the initial rounds of screening, in which the potency of the protein-fragment interaction is less important than the geometry of that interaction...