High-content screen of a covalent library finds new early mitotic inhibitors
- A cell-based high-content imaging screen was built to catch early mitotic spindle assembly defects.
- Run against a 3,520-compound cysteine-reactive library, it found a microtubule depolymerizer, a spindle-positioning disruptor and compounds that disturb spindle structure and chromosome alignment.
- Two hits caused mitotic arrest and reduced cancer cell viability (preprint; not yet peer reviewed).
💡 Points
Phenotypic screening with a covalent library is a sensible way to find chemotypes that target-based approaches would never pick. The weak point is deconvolution: until the cysteine targets are identified, a microtubule depolymerizer risks being one more tubulin binder. Worth tracking for the non-tubulin hits.
Identification of Cysteine-Reactive Early Mitotic Inhibitors ↗