Dolastatin 15, a depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the anti-tubulin agent Dolastatin 10. Dolastatin 15 can be used as an ADC cytotoxin and it induces cell cycle arrest and apoptosis in multiple myeloma cells.

Dolastatin 15 shows growth inhibitory activity against all four SCLC cell lines (NCI-H69, NCI-H82, NCI-H345, NCI-H446) (IC50: 0.039-28.8 nM), which were 2.7-9.2-fold higher than the values for dolastatin 10. Dolastatin 15 induces cell cycle arrest at the G2/M phase followed by apoptosis in various human myeloma cell lines (RPMI8226, U266, and IM9) and it also induces apoptosis of myeloma cells via activation of both mitochondrial- and Fas (CD95)/Fas-L (CD95-L)-mediated pathways [2]. All four SCLC cell lines underwent G2/M arrest within 24 hours of exposure to dolastatin 15 [4].

Dolastatin 15, through a non-cleavable linker, is conjugated to Trastuzumab at the drug's C-terminus lysine residues. The resulting compound, Trastuzumab-amide-C-term-Dol15, inhibits the growth of cells with high HER2 expression (i.e., SK-BR-3, SK-OV-3) in a target-dependent manner in vitro. Furthermore, this antibody-drug conjugate (ADC) demonstrates efficacy at various doses (i.e., 10 and 20 mg/kg) in a SK-OV-3 human ovarian cancer xenograft model [3].