Dolastatin 15 is a peptide that has been found in D. auricularia and has anticancer activity. It induces cell cycle arrest at the G/M phase and inhibits proliferation of JVM-2 and EHEB human B cell leukemia cells when used at a concentration of 1 nM. Dolastatin 15 also inhibits proliferation of RPMI-8826, U266, and IM-9 human multiple myeloma cells (ICs = 0.5-1 nM), as well as a panel of colon and ovarian cancer cell lines (ICs = 0.031-1.8 nM). It reduces tumor growth in a CH1 mouse xenograft model when administered at a dose of 5.25 mg/kg per day.
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]
体外研究
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.
体内研究
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.
分子式
C45H68N6O9
分子量
837.05646
CAS号
123884-00-4
中文名称
Dolastatin 15
运输条件
Room temperature in continental US; may vary elsewhere.