What is Monomethyl Auristatin E (MMAE)?

Monomethyl Auristatin E

Chemical Name: (S)-N-((3R,4S,5S)-1-((S)-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,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamide
Molecular Weight: 717.98
Formula: C39H67N5O7
CAS: 474645-27-7
Solubility: DMSO up to 20 mM

Biological Activity
Monomethyl auristatin E (MMAE, vedotin) is a very potent antimitotic agent that inhibits cell division by blocking the polymerisation of tubulin. [1,2,3] The family of auristatins are synthetic analogues of the antineoplastic natural product Dolastatin 10,  ultrapotent cytotoxic microtubule inhibitors that are clinically used as payloads in antibody-drug conjugates. [6][7]

Monomethyl auristatin E or MMAE is 100-1000 times more potent than doxorubicin(Adriamycin/Rubex) and cannot be used as a drug itself. However, as part of an antibody-drug conjugate or ADC, MMAE is linked to a monoclonal antibody (mAb) that recognizes a specific marker expression in cancer cells and directs MMAE to a specific, targeted cancer cell.

ADC Bio
MabPlex
Lonza
 

The linker linking MMAE to the monoclonal antibody is stable in extracellular fluid, but is cleaved by cathepsin once the antibody-drug-conjugate has bound to the targeted cancer cell antigen and entered the cancer cell, after which the ADC releases the toxic MMAE and activates the potent anti-mitotic mechanism. Antibody-drug conjugates enhance the antitumor effects of antibodies and reduce adverse systemic effects of highly potent cytotoxic agents.[2,3,4,5]