Dolastatin 15 is a seven-subunit depsipeptide natural product isolated from the sea hare Dolabella auricularia, a potent antimitotic agent structurally related to dolastatin 10. It binds weakly in the vinca domain of tubulin with an apparent dissociation constant of approximately 30 µM, inhibiting tubulin polymerization with an IC₅₀ of 23 µM—notably less potent than its peptide counterpart at 1.2 µM. Despite this modest in vitro activity against tubulin, it exhibits strong cytotoxicity against cell lines such as L1210 murine leukemia and human Burkitt lymphoma, with IC₅₀ values in the low nanomolar range (3–5 nM) and causes mitotic arrest at toxic concentrations. Its unique profile makes it a valuable tool for studying tubulin-binding domains and a core component in the design of antibody conjugates targeting specific cancer cell surface receptors.

DLS 15