MMAF | Monomethyl auristatin F | CAS#745017-94-1

MedKoo Cat#: 407222 | Name: MMAF (Monomethyl auristatin F)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Monomethyl auristatin F (MMAF) is a potent tubulin polymerization inhibitor. It is part of some experimental anti-cancer antibody-drug conjugates such as vorsetuzumab mafodotin and SGN-CD19A. In International Nonproprietary Names for MMAF-antibody-conjugates, the name mafodotin refers to MMAF plus its attachment structure to the antibody. MMAF is actually desmethyl-auristatin F; that is, the N-terminal amino group has only one methyl substituent instead of two as in auristatin F itself.

Chemical Structure

MMAF (Monomethyl auristatin F)

CAS#745017-94-1

Theoretical Analysis

MedKoo Cat#: 407222

Name: MMAF (Monomethyl auristatin F)

CAS#: 745017-94-1

Chemical Formula: C39H65N5O8

Exact Mass: 731.4833

Molecular Weight: 731.98

Elemental Analysis: C, 64.00; H, 8.95; N, 9.57; O, 17.49

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 315.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship

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Related CAS #

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Synonym

Monomethyl auristatin F; MMAF; desmethyl-auristatin F;

IUPAC/Chemical Name

((2R,3R)-3-((2S)-1-((3R,5S)-4-((S)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L-phenylalanine

InChi Key

MFRNYXJJRJQHNW-NARUGQRUSA-N

InChi Code

InChI=1S/C39H65N5O8/c1-12-25(6)34(43(9)38(48)33(24(4)5)42-37(47)32(40-8)23(2)3)30(51-10)22-31(45)44-20-16-19-29(44)35(52-11)26(7)36(46)41-28(39(49)50)21-27-17-14-13-15-18-27/h13-15,17-18,23-26,28-30,32-35,40H,12,16,19-22H2,1-11H3,(H,41,46)(H,42,47)(H,49,50)/t25-,26+,28-,29-,30+,32-,33-,34?,35+/m0/s1

SMILES Code

O=C([C@H](CC1=CC=CC=C1)NC([C@H](C)[C@H]([C@@H]2CCCN2C(C[C@@H](OC)C(N(C)C([C@@H](NC([C@H](C(C)C)NC)=O)C(C)C)=O)[C@@H](C)CC)=O)OC)=O)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Monomethyl auristatin F (MMAF) is an antitubulin agent that inhibits cell division by blocking the polymerization of tubulin. 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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB60810

QC Data

View QC data: current batch, Lot#CRB60810

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

MMAF is an antineoplastic agent and a tubulin polymerization inhibitor.

In vitro activity:

Metabolite profiling study of MMAF was performed in vitro using rat and human liver microsomes fortified with NADPH, UDPGA, and GSH. There were four kinds of metabolites of MMAF. They are characterized by mono-oxidation, demethylation, di-demethylation, loss of C6H11NO. Each of the characterized metabolites had various sites of metabolism (Figure 6). These results suggest that the major metabolic pathway of MMAF is demethylation. Under the current experimental conditions, four metabolites and seven metabolites were tentatively identified in rat and human liver microsomes, respectively. This phenomenon would be due to the difference in metabolic enzymes between rat and human. In conclusion, these results will be helpful to understand the PK, catabolism, and metabolism behavior of MMAF comprehensively when developing ADCs in the future. Reference: Molecules. 2019 Jul 29;24(15):2754. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696338/

In vivo activity:

To formulate GPC-1-ADC, MMAF was conjugated with anti-GPC-1 mAb. MMAF inhibits mitosis by suppressing tubulin polymerisation and disrupting the microtubule network in proliferating cells. MMAF has potent antitumour effects when it is conjugated via a protease-cleavable linker to a monoclonal antibody that targets internalised tumour-specific cell surface antigens. The linker to the monoclonal antibody is stable in extracellular fluid, but the conjugate is cleaved by cathepsin B upon entry into the tumour cells. Thence, it activates the antimitotic mechanism. GPC-1-ADC had a significant antitumour effect in BxPC-3-xenografted and PDX mice. Reference: Br J Cancer. 2020 Apr;122(9):1333-1341. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189381/

	Solvent	mg/mL	mM
Solubility
	DMSO	62.5	85.38
	DMSO:PBS (pH 7.2) (1:6)	0.1	0.19
	DMF	10.0	13.66
	Ethanol	51.0	69.67
	Water	100.0	136.62

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 731.98 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Park MH, Lee BI, Byeon JJ, Shin SH, Choi J, Park Y, Shin YG. Pharmacokinetic and Metabolism Studies of Monomethyl Auristatin F via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry. Molecules. 2019 Jul 29;24(15):2754. doi: 10.3390/molecules24152754. PMID: 31362431; PMCID: PMC6696338. 2. Nishigaki T, Takahashi T, Serada S, Fujimoto M, Ohkawara T, Hara H, Sugase T, Otsuru T, Saito Y, Tsujii S, Nomura T, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Nakajima K, Eguchi H, Yamasaki M, Mori M, Doki Y, Naka T. Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer. Br J Cancer. 2020 Apr;122(9):1333-1341. doi: 10.1038/s41416-020-0781-2. Epub 2020 Mar 10. PMID: 32152502; PMCID: PMC7189381.

In vitro protocol:

In vivo protocol:

1. Nishigaki T, Takahashi T, Serada S, Fujimoto M, Ohkawara T, Hara H, Sugase T, Otsuru T, Saito Y, Tsujii S, Nomura T, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Nakajima K, Eguchi H, Yamasaki M, Mori M, Doki Y, Naka T. Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer. Br J Cancer. 2020 Apr;122(9):1333-1341. doi: 10.1038/s41416-020-0781-2. Epub 2020 Mar 10. PMID: 32152502; PMCID: PMC7189381.

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