Description
Monomethyl Auristatin E (MMAE) is a synthetic analog of dolastatin 10 that similarly inhibits tubulin polymerization and exhibits potent cytotoxicity. It is commonly conjugated with monoclonal antibodies directed at antigens specific to cancer cells for tumor-directed cytotoxicity.
Synonyms
MMAE; Vedotin; Monomethyl auristatin E; Monomethylauristatin E; N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide
IUPAC Name
(2S)-N-[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamide
Canonical SMILES
CC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(C)C(C2=CC=CC=C2)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC
InChI
InChI=1S/C39H67N5O7/c1-13-25(6)34(43(10)39(49)33(24(4)5)42-38(48)32(40-9)23(2)3)30(50-11)22-31(45)44-21-17-20-29(44)36(51-12)26(7)37(47)41-27(8)35(46)28-18-15-14-16-19-28/h14-16,18-19,23-27,29-30,32-36,40,46H,13,17,20-22H2,1-12H3,(H,41,47)(H,42,48)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1
InChIKey
DASWEROEPLKSEI-UIJRFTGLSA-N
Density
1.088±0.06 g/cm3 (Predicted)
Solubility
Soluble in DMSO (Slightly), Methanol (Slightly, Sonicated); Insoluble in Water
Melting Point
>90°C (dec.)
Flash Point
482.1±34.3 °C
Index Of Refraction
1.519
Vapor Pressure
0.0±0.3 mmHg at 25°C
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. MMAE sensitizes 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.
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 prolongs tumor regression in xenograft models.
Clinical Trial Information
NCT Number | Condition Or Disease | Phase | Start Date | Sponsor | Status |
NCT05113459 | Gastric Cancer | Phase 2 | 2021-11-09 | Guoxin Li | Not yet recruiting |
NCT03187210 | Lymphoma | Phase 1, Phase 2 | 2021-08-05 | University Hospital Inselspital, Berne | Recruiting |
NCT04679012 | Richter Syndrome | Phase 2 | 2021-09-22 | Weill Medical College of Cornell University | Not yet recruiting |
NCT05006664 | Lymphoma, T-Cell, Peripheral | Phase 2 | 2021-09-01 | Czech Lymphoma Study Group | Not yet recruiting |
NCT02227433 | Hodgkin Lymphoma | Phase 2 | 2020-12-22 | Fondazione Italiana Linfomi ONLUS | Completed |
Application
ADCs Cytotoxin
Appearance
White to Off-white Solid
Storage
Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)
Pictograms
Irritant; Health Hazard
Boiling Point
873.5±65.0 °C at 760 mmHg