VCMMAE 是一种用于 ADC 的药物-接头偶联物，具有抗癌活性，它由 MMAE和 Vc 连接而成。

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

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, owing to its membrane permeability, it has the ability 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 increased DNA damage signaling and activation of CHK1 that delay the tumor growth. Tumor-targeted ACPP-cRGD-MMAE with IR produces a more robust and significantly prolonged tumor regression in xenograft models.

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.

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.

646502-53-6

C68H105N11O15

1316.65

mc-vc-PAB-MMAE

DMSO:54 mg/mL,VcmMAE is dissolved inDMSO and then diluted with 0.9% NaCl
Powder: -20°C for 3 years
In solvent: -80°C for 2 years