Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site

Significance Natural products provide the inspiration for most drugs, and marine natural products, in particular, are emerging as promising new therapeutics with targets or mechanisms of action. Pharmacological targeting tubulin dynamics has been a validated strategy cancer therapy decades, yielding structurally diverse derivatives, including paclitaxel, vincristine, maytansine, eribulin, six known different binding sites. We discovered chemical scaffold from cyanobacteria that seventh site. report entire spectrum biological novelties, isolation, structure determination, synthesis product, investigation its mechanism action, target identification, mode elucidation at atomic level.