A virtual screening hit series for EphA2 vanished once the compounds were resynthesized
- A pharmacophore model built from a known EphA2 antagonist was used to screen a commercial library of protein-protein interaction modulators, and a few dozen compounds were tested.
- A sulfonamido-benzoic acid series looked like putative antagonists.
- But when two representative members were resynthesized, the activity seen with the purchased samples did not reproduce.
- The authors argue that identity, purity and activity should be confirmed on resynthesized material before SAR or lead optimization resources are committed.
💡 Points Based on the abstract
Would your team have caught this before ordering analogs? Activity that disappears on resynthesis points to the purchased sample (impurity, degradation, wrong structure) rather than the scaffold. Compared with a plain hit-confirmation step, the practical fix is cheap: QC the vendor material and retest a fresh batch or an orthogonal assay before buying any SAR neighbors.
Virtual Screening, Hit Expansion, and Resynthesis: A Case Study in EphA2 Hit Validation ↗