Name: MMAF
Brand: BOC Sciences
Price: 358 USD
Availability: MadeToOrder

Synonyms

Monomethylauristatin F; Monomethyl Auristatin F; N-Methyl-L-valyl-L-valyl-(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl-(αR,βR,2S)-β-methoxy-α-methyl-2-pyrrolidinepropanoyl-L-phenylalanine; Monomethylauristatin Phenylalanine; L-Valinamide, N-methyl-L-valyl-N-[(1S,2R)-4-[(2S)-2-[(1R,2R)-3-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-methoxy-2-methyl-3-oxopropyl]-1-pyrrolidinyl]-2-methoxy-1-[(1S)-1-methylpropyl]-4-oxobutyl]-N-methyl-; ((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-methylpropanoyl)-L-phenylalanine

IUPAC Name

(2S)-2-[[(2R,3R)-3-methoxy-3-[(2S)-1-[(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid

Canonical SMILES

CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC

InChI

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

InChIKey

MFRNYXJJRJQHNW-DEMKXPNLSA-N

Density

1.116±0.06 g/cm3 (Predicted)

Solubility

Soluble in DMF (Slightly), DMSO (Slightly), Methanol (Slightly), Water (Slightly)

Melting Point

>137°C (dec.)

Flash Point

496.2±34.3 °C

Index Of Refraction

1.522

PSA

173.59000

Vapor Pressure

0.0±0.3 mmHg at 25°C

Appearance

White to Off-white Solid

Shelf Life

≥12 months if stored properly

Shipping

Room temperature

Storage

Store at 2-8°C under inert atmosphere

Boiling Point

896.8±65.0 °C at 760 mmHg

In Vitro

MMAF (Monomethylauristatin F) shows in vitro cytotoxicity against a panel of cell lines. The IC50 values for Karpas 299, H3396, 786-O and Caki-1 are 119, 105, 257, and 200 nM, respectively. Targeted MMAF (Monomethylauristatin F) is much more potent than the free drug, and that cAC10 conjugates of MMAF (Monomethylauristatin F) display pronounced activities. On a molar basis, the cAC10-L1-MMAF4 is an average of over 2200-fold more potent than free MMAF (Monomethylauristatin F) and is active on all the CD30-positive cell lines tested.

In Vivo

The maximum tolerated dose in mice of MMAF (Monomethylauristatin F) (>16 mg/kg) is much higher than MMAF (Monomethylauristatin F) (1 mg/kg). cAC10-L1-MMAF4 has an MTD of 50 mg/kg in mice and 15 mg/kg in rats. The corresponding cAC10-L4-MMAF4 ADC was much less toxic, having MTDs in mice and rats of >150 mg/ kg and 90 mg/kg in rats, respectively.

MMAF (Monomethyl Auristatin F) is a synthetic analog of dolastatin 10 and a widely recognized ADC cytotoxin used as an ADC payload in antibody-drug conjugates. As a potent microtubule-disrupting agent, MMAF binds to tubulin and inhibits polymerization, leading to cell cycle arrest and apoptosis. Compared to its analog MMAE (Monomethyl Auristatin E), MMAF contains a charged C-terminal phenylalanine residue that reduces membrane permeability, resulting in higher selectivity and reduced systemic toxicity.

Within antibody-drug conjugates, MMAF is typically linked to monoclonal antibodies via stable, non-cleavable linkers. This design ensures that MMAF remains inactive in circulation and only exerts its cytotoxic activity after ADC internalization and lysosomal degradation inside tumor cells. Such a mechanism enhances therapeutic precision by confining the cytotoxic effect to targeted cancer cells while minimizing off-target damage. Its stability in plasma and controlled release make MMAF a highly reliable payload option for oncology-focused ADC platforms.

Applications of MMAF include its integration into multiple clinical-stage ADC candidates targeting hematological malignancies and solid tumors, such as multiple myeloma, lymphoma, and breast cancer. It has been studied in constructs conjugated to antibodies against CD30, CD79b, and other tumor-associated antigens. The unique pharmacological properties of MMAF, including its reduced bystander effect compared with MMAE, make it particularly suitable for applications where precise tumor targeting is essential. Researchers continue to explore MMAF in novel linker-payload systems to further optimize stability, intracellular release, and therapeutic outcomes in next-generation antibody-drug conjugates.

1.Improved efficacy of alphavbeta3-targeted albumin conjugates by conjugation of a novel auristatin derivative.

Temming K;Meyer DL;Zabinski R;Senter PD;Poelstra K;Molema G;Kok RJ Mol Pharm. 2007 Sep-Oct;4(5):686-94. Epub 2007 Aug 8.

Cellular handling of drug delivery preparations en route to the lysosomal compartment has been extensively studied, but little is known about cellular handling of drugs subsequent to their release from the delivery system. We studied a series of closely related drug targeting conjugates, consisting of albumins equipped with alpha vbeta 3-selective RGD-peptide homing ligands, PEG stealth domains, and either the antitubulin agent monomethyl auristatin E (MMAE) or a new F-variant (MMAF). Since MMAF has a C-terminal charge, this compound is potentially less prone to passive redistribution after its release from the carrier. We demonstrate that RGD-peptide-equipped albumin conjugates with MMAF were indeed more potent than MMAE conjugates, in killing both alpha vbeta 3-positive tumor cells and proliferating endothelial cells. Efficacy increased more in tumor cells than in endothelial cells, suggesting different drug redistribution behavior for the two cell types. Binding affinity and uptake of the conjugate and the cellular handling of released drug contributed to the final efficacy of drug-carrier conjugates, highlighting the importance of all aspects to be carefully considered in the design of targeted drug delivery preparations.

2.Characterization of ABBV-221, a Tumor-Selective EGFR-Targeting Antibody Drug Conjugate.

Phillips AC;Boghaert ER;Vaidya KS;Falls HD;Mitten MJ;DeVries PJ;Benatuil L;Hsieh CM;Meulbroek JA;Panchal SC;Buchanan FG;Durbin KR;Voorbach MJ;Reuter DR;Mudd SR;Loberg LI;Ralston SL;Cao D;Gan HK;Scott AM;Reilly EB Mol Cancer Ther. 2018 Apr;17(4):795-805. doi: 10.1158/1535-7163.MCT-17-0710. Epub 2018 Feb 26.

Depatuxizumab mafodotin (depatux-m, ABT-414) is a tumor-selective antibody drug conjugate (ADC) comprised of the anti-EGFR antibody ABT-806 and the monomethyl auristatin F (MMAF) warhead. Depatux-m has demonstrated promising clinical activity in glioblastoma multiforme (GBM) patients and is currently being evaluated in clinical trials in first-line and recurrent GBM disease settings. Depatux-m responses have been restricted to patients with amplified EGFR, highlighting the need for therapies with activity against tumors with nonamplified EGFR overexpression. In addition, depatux-m dosing has been limited by corneal side effects common to MMAF conjugates. We hypothesized that a monomethyl auristatin E (MMAE) ADC utilizing an EGFR-targeting antibody with increased affinity may have broader utility against tumors with more modest EGFR overexpression while mitigating the risk of corneal side effects. We describe here preclinical characterization of ABBV-221, an EGFR-targeting ADC comprised of an affinity-matured ABT-806 conjugated to MMAE. ABBV-221 binds to a similar EGFR epitope as depatux-m and retains tumor selectivity with increased binding to EGFR-positive tumor cells and greater ;in vitro; potency.

3.A human antibody-drug conjugate targeting EphA2 inhibits tumor growth in vivo.

Jackson D;Gooya J;Mao S;Kinneer K;Xu L;Camara M;Fazenbaker C;Fleming R;Swamynathan S;Meyer D;Senter PD;Gao C;Wu H;Kinch M;Coats S;Kiener PA;Tice DA Cancer Res. 2008 Nov 15;68(22):9367-74. doi: 10.1158/0008-5472.CAN-08-1933.

The EphA2 receptor tyrosine kinase is selectively expressed on the surface of many different human tumors. We have previously shown that tumor cells can be targeted by EphA2 monoclonal antibodies and that these antibodies function, in part, by inducing EphA2 internalization and degradation. In this report, we describe the isolation and characterization of a fully human monoclonal antibody (1C1) that selectively binds both the human and rodent EphA2 receptor. After cell binding, the antibody induces rapid tyrosine phosphorylation, internalization, and degradation of the EphA2 receptor. Because monoclonal antibodies that selectively bind tumor cells and internalize provide a vehicle for targeted delivery of cytotoxics, 1C1 was conjugated to the microtubule inhibitor monomethylauristatin phenylalanine using a stable maleimidocaproyl linker. The anti-EphA2 antibody-drug conjugate [1C1-maleimidocaproyl-MMAF (mcMMAF)] stimulated the activation of caspase-3/caspase-7 and the death of EphA2-expressing cells with IC(50) values as low as 3 ng/mL. Similarly, the conjugate induced degradation of the EphA2 receptor and inhibited tumor growth in vivo. Administration of 1C1-mcMMAF at doses as low as 1 mg/kg once weekly resulted in significant growth inhibition of EphA2-expressing tumors without any observable adverse effects in mouse xenograft and rat syngeneic tumor models.

HPLC

What is MMAF?

MMAF (Monomethyl auristatin F) is a synthetic antimitotic agent used as a cytotoxic payload in ADCs. It binds tubulin and inhibits microtubule polymerization, providing a reliable mechanism for targeted cytotoxicity in cancer research models.

25/7/2022

Could you explain how MMAF works in ADC applications?

MMAF is conjugated to antibodies to ensure selective delivery. Once internalized, it disrupts the microtubule network, causing cell cycle arrest and apoptosis. Its non-permeable nature reduces off-target effects in experimental systems.

21/2/2021

Could you advise which linkers are compatible with MMAF?

MMAF is commonly conjugated via non-cleavable linkers such as maleimidocaproyl or other thioether-based chemistries. The linker type affects intracellular release and overall ADC stability.

10/10/2022

Could you please let me know if BOC Sciences can customize MMAF ADCs?

BOC Sciences offers custom ADC solutions with MMAF, including conjugation optimization, linker chemistry selection, and analytical characterization to support preclinical studies and research applications.

15/9/2018

Good morning! What forms of MMAF are available for research applications?

MMAF is supplied in laboratory-appropriate formats, including lyophilized powder or pre-dissolved solutions, along with handling and storage instructions to ensure compatibility with ADC development workflows.

5/4/2022

— Dr. Brian Taylor, Senior Scientist (USA)

MMAF delivered with high purity and consistent performance. Technical support helped optimize conjugation protocols.

10/10/2022

— Dr. Laura Evans, Research Fellow (UK)

Excellent product quality and quick delivery. MMAF was critical for our ADC cytotoxicity studies.

5/4/2022

— Dr. Michael Braun, Medicinal Chemist (Germany)

Reliable supply and clear QC documentation. BOC Sciences facilitated our ADC projects efficiently.

15/9/2018

— Dr. Emily Grant, Biochemist (Canada)

High-quality MMAF supported our in vitro cytotoxicity assays seamlessly.