Dolastatin 15 (DLS 15), a depsipeptide derived fromDolabella auricularia, is a potentantimitoticagent structurally related to the antitubulin agent Dolastatin 10. Dolastatin 15 induces cell cycle arrest andapoptosisin multiple myeloma cells. Dolastatin 15 can be used as anADC cytotoxin^[1][2][3].

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^[2]. Dolastatin 15 (DLS 15) displays growth inhibitory activity against all four SCLC cell lines (NCI-H69, NCI-H82, NCI-H345, NCI-H446) with IC₅₀values 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^[4].

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^[3].

837.06

C₄₅H₆₈N₆O₉

123884-00-4

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