VcMMAE

Names

[ Name ]:
VcMMAE

[Synonym ]:
L-Ornithinamide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]-L-valyl-N-(aminocarbonyl)-N-[4-[(5S,8S,11S,12R)-12-[2-[(2S)-2-[(1R,2R)-3-[[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]amino]-1 -methoxy-2-methyl-3-oxopropyl]-1-pyrrolidinyl]-2-oxoethyl]-4,10-dimethyl-5,8-bis(1-methylethyl)-11-[(1S)-1-methylpropyl]-3,6,9-trioxo-2,13-dioxa-4,7,10-triazatetradec-1-yl]phenyl]-
N-[6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-L-valyl-N-{4-[(5S,8S,11S,12R)-11-[(2S)-2-butanyl]-12-(2-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenyl-2-propanyl]amino}-1-methoxy-2-methyl-3-oxop ;ropyl]-1-pyrrolidinyl}-2-oxoethyl)-5,8-diisopropyl-4,10-dimethyl-3,6,9-trioxo-2,13-dioxa-4,7,10-triazatetradec-1-yl]phenyl}-N-carbamoyl-L-ornithinamide
Vedotin
Maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl auristatin E
VcMMAE

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Antibody-drug Conjugate >> Drug-Linker Conjugates for ADC

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Cancer

[In Vitro]

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].

[In Vivo]

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].

[Cell Assay]

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.

[Animal admin]

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.

[References]

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
1347.6±65.0 °C at 760 mmHg

[ Molecular Formula ]:
C₆₈H₁₀₅N₁₁O₁₅

[ Molecular Weight ]:
1316.626

[ Flash Point ]:
768.8±34.3 °C

[ Exact Mass ]:
1315.779175

[ LogP ]:
6.04

[ Vapour Pressure ]:
0.0±0.3 mmHg at 25°C

[ Index of Refraction ]:
1.556

[ Storage condition ]:
2-8℃

VcMMAE

Names

Biological Activity

Chemical & Physical Properties

Related Compounds