Monomethyl auristatin E (MMAE)

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]  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. 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]

Reference
[1] Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. Epub 2003 Apr 24.
[2] Junutula JR, Raab H, Clark S, Bhakta S, Leipold DD, Weir S, Chen Y, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol. 2008 Aug;26(8):925-32. doi: 10.1038/nbt.1480. Epub 2008 Jul 20.
[3] Asundi J, Reed C, Arca J, McCutcheon K, Ferrando R, Clark S, Luis E, Tien J, et al. An antibody-drug conjugate targeting the endothelin B receptor for the treatment of melanoma. Clin Cancer Res. 2011 Mar 1;17(5):965-75. doi: 10.1158/1078-0432.CCR-10-2340. Epub 2011 Jan 18.
[4] Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, et al. Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. doi: 10.1200/JCO.2011.38.0410. Epub 2012 Mar 26.
[5] Monomethyl auristatin E (WikiPedia

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