Identification of seco‐clavilactone B as a small‐molecule actin polymerization inhibitor

Phenotype‐based chemical screening is an attractive strategy for the identification of bioactive compounds. We searched for a compound that induces cellular morphological change and identified a novel compound that we named seco‐clavilactone B (Seco‐CB). Treatment with Seco‐CB decreased the ratio of filament actin (F‐actin) to globular actin (G‐actin). An in vitro actin polymerization assay revealed that Seco‐CB inhibited actin polymerization directly. Further analysis demonstrated that the inhibitory effect of Seco‐CB on actin polymerization was associated with Seco‐CB binding to either Thr5 or Cys285 of actin. These data indicate that Seco‐CB is a novel actin polymerization inhibitor.