VcMMAE (mc-vc-PAB-MMAE) is a drug-linker conjugate for ADC with potent antitumor activity by using the anti-mitotic agent, monomethyl auristatin E (MMAE, a tubulin inhibitor), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc).

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^[1]. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule and dose dependent manner correlating with mitotic arrest. Radiosensitization is evidenced by decreased clonogenic survival and increased DNA double strand breaks in irradiated cells^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

1316.63

C₆₈H₁₀₅N₁₁O₁₅

646502-53-6

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years

*该产品在溶液状态不稳定，建议您现用现配，即刻使用。

In Vitro: 

DMSO : ≥ 54 mg/mL (41.01 mM)

* “≥” means soluble, but saturation unknown.

*

请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现用现配，即刻使用。

In Vivo:

• 1.

  VcMMAE is dissolved in DMSO and then diluted with 0.9% NaCl^[3].

• [1]. Okeley, et al. Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate. Clinical Cancer Research (2010), 16(3), 888-897.

  [2]. Lisa Buckel, et al. Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery. Cancer Res. 2015 Apr 1;75(7):1376-87.

  [3]. Jianmin Fang, et al. Anti-her2 antibody and conjugate thereof. US 20160304621 A1.

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

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Okeley, et al. Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate. Clinical Cancer Research (2010), 16(3), 888-897.

  [2]. Lisa Buckel, et al. Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery. Cancer Res. 2015 Apr 1;75(7):1376-87.

  [3]. Jianmin Fang, et al. Anti-her2 antibody and conjugate thereof. US 20160304621 A1.