Monomethyl Auristatin F

Chemical Name: (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoic acid

Molecular Weight: 731.96
Formula: C39H65N5O8
CAS#: 141205-32-5
Solubility: DMSO up to 20 mM

Biological Activity
Monomethyl auristatin F (MMAF) is an antitubulin agent agent that inhibits cell division by blocking the polymerization of tubulin. It is a new auristatin derivative with a charged C-terminal phenylalanine that attenuates its cytotoxic activity compared to its uncharged counterpart, monomethyl auristatin E (MMAE). [1, 2, 3, 4] Because of MMAF is highly toxic, it cannot be used as a drug itself.  MMAF induces potent antitumor effects when conjugated via protease cleavable linkers to a monoclonal antibody targeting internalizing, tumor-specific cell surface antigens. The linker to the monoclonal antibody is stable in extracellular fluid, but is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the anti-mitotic mechanism. [4, 5]

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References

[1] Smith LM, Nesterova A, Alley SC, Torgov MY, Carter PY. Potent cytotoxicity of an auristatin-containing antibody-drug conjugate targeting melanoma cells expressing melanotransferrin/p97. Mol Cancer Ther June 2006 5; 1474-82.doi: 10.1158/1535-7163.MCT-06-0026[2] Doronina SO, Mendelsohn BA, Bovee TD, Cerveny CG, Alley SC, Meyer DL, Oflazoglu E, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006 Jan-Feb;17(1):114-24.[3] Oflazoglu E, Stone IJ, Gordon K, Wood CG, Repasky EA, Grewal IS, Law CL, Gerber HP. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res. 2008 Oct 1;14(19):6171-80. doi: 10.1158/1078-0432.CCR-08-0916. Epub 2008 Sep 22.[4] Nilsson R, Mårtensson L, Eriksson SE, Sjögren HO, Tennvall J. Toxicity-reducing potential of extracorporeal affinity adsorption treatment in combination with the auristatin-conjugated monoclonal antibody BR96 in a syngeneic rat tumor model. Cancer. 2010 Feb 15;116(4 Suppl):1033-42. doi: 10.1002/cncr.24790.

[5] Monomethyl auristatin E (Wikipedia)

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ADC Review, Journal of Antibody-drug Conjugates (ISSN 2327-0152) launched in 2013, is designed to serve the needs of a diverse community of individuals including academia, life sciences, pharma, (basic, translational and clinical) research, clinicians/physicians, along with regulatory affairs, government authorities and representatives from payers, and policy makers. The Journal’s content includes peer reviewed research, commentaries, news features, discussions, editorials and blogs on topics relevant to a broad international readership. The Journal also offers a knowledge center (called ADC University) offering the latest and most relevant information about Antibody-drug Conjugates (ADCs), BiSpecific Antibodies, Site Specific Antibody Drug Conjugates, Small Molecule Drug Conjugates (SMDC), and Engineered Antibody Fragments. The purpose of the Journal is to present this information in an understandable and a useful format for all stakeholders.