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VcMMAE is a drug-linker conjugate for ADC with potent antitumor activity. 

Microtubule/Tubulin

MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule and dose dependent manner correlating with mitotic arrest. Monomethyl auristatin E (MMAE) is efficiently released from SGN-35 within CD30+ cancer cells and, due to its membrane permeability, is able to exert cytotoxic activity on bystander cells. Radiosensitization is evidenced by decreased clonogenic survival and increased DNA double strand breaks in irradiated cells. 

Monomethyl auristatin E (MMAE) in combination with IR results in tumor growth delay, tumor-targeted ACPP-cRGD-MMAE with IR produces a more robust and significantly prolonged tumor regression in xenograft models. 

6-8 week old female athymic nu/nu mice are injected subcutaneously into thighs with 5×106 HCT-116 or PANC-1 cells in a 1:1 Matrigel and PBS solution. Mice are treated with IR or intravenous (IV) injection of ACPP-cRGD-MMAE (6 nmoles/day, 18 nmoles total, i.v.), tumor tissue is harvested, formalin fixed and paraffin embedded followed by staining with indicated antibodies. The primary antibody is used at a 1:250 dilution and is visualized using DAB as a chromagen with the UltraMap system. 

Monomethyl auristatin E is reconstituted in DMSO at a concentration of 5 nM. Monomethyl auristatin E (MMAE, 5 nM) and ionizing radiation (IR) treated cells are harvested and lysed in RIPA buffer with protease and phosphatase inhibitors. 30 μg of lysate undergo electrophoresis using 4-12% Bis-Tris gels, transferred to PVDF membranes and incubated with indicated primary antibodies. 

 mc-vc-PAB-MMAE , 化合物VCMMAE mc-vc-PAB-MMAE 

98%

646502-53-6 

For research use only .