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A Brief Introduction of MMAE(Monomethyl Auristatin E, Vedotin)

What's MMAE?
Monomethyl auristatin E (abbr. MMAE, commercial name as Vedotin) is a synthetic antineoplastic agent. It cannot be used as a drug itself due to its high toxicity, normally it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells.


Structure of MMAE:
Please refer to: MMAE | Monomethyl Auristatin E
MMAE is actually desmethyl-auristatin E; that is, the N-terminal amino group has only one methyl substituent instead of two as in auristatin E itself.


Toxicity of MMAE:
IC50 of proliferation/viability of tumor cell lines are in the range of 10-7-10-10 M for MMAF/ MMAE auristatin derivatives.


MMAE mechanism of action:
MMAE inhibits cell division by blocking the polymerisation of tubulin as antimitotic agent in ADCs(Antibody Drug Conjugates).


FDA approved ADCs drugs with MMAE:
Adcetris (brentuximab vedotin) is an ADC comprised of a chimeric anti-CD30 antibody (cAC10) conjugated through interchain disulfide bonds to monomethyl auristatin E (MMAE) via a valine-citrulline dipeptide cleavable linker, with
an average DAR of 4.The FDA approval of Adcetris (brentuximab vedotin, Seattle Genetics) in 2011. Adcetris is an antibody-drug conjugate (ADC) directed to the protein CD30, which is expressed in classical Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL).


Commercial Availability of MMAE:
MMAE is obtained from total synthesis and now available in the market.

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