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Dolastatin 15, a depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent Dolastatin 10. Dolastatin 15 induces cell cycle arrest and apoptosis in multiple myeloma cells. Dolastatin 15 can be used as an ADC cytotoxin.[1]

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

Dolastatin 15 conjugates to Trastuzumab via lysine residues at the drug C-terminus using a non-cleavable linker (Trastuzumab-amide-C-term-Dol15) produced target-dependent growth inhibition of cells endogenously expressing high HER2 levels (i.e., SK-BR-3, SK-OV-3) in vitro. This ADC was effective at varying doses (i.e., 10 and 20 mg/kg) in the SK-OV-3 human ovarian cancer xenograft.

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