Name: Mc-MMAF
Brand: BOC Sciences
Price: 519 USD
Availability: MadeToOrder

Synonyms

SGD-1269; SGD 1269; SGD1269; mc-MMAF; mcMMAF; L4-MMAF; Maleimidocaproyl-MMAF; Maleimidocaproyl monomethylauristatin F; Mafodotin.((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylhexanamido)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L-phenylalanine

IUPAC Name

(2S)-2-[[(2R,3R)-3-[(2S)-1-[(3R,4S,5S)-4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoyl-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl]amino]-3-phenylpropanoic acid

Canonical SMILES

O=C(O)[C@H](CC1=CC=CC=C1)NC([C@H](C)[C@H]([C@H]2N(C(C[C@@H](OC)[C@@H](N(C)C([C@@H](NC([C@@H](N(C)C(CCCCCN3C(C=CC3=O)=O)=O)C(C)C)=O)C(C)C)=O)[C@@H](C)CC)=O)CCC2)OC)=O

InChI

InChI=1S/C49H76N6O11/c1-12-32(6)44(37(65-10)29-41(59)54-27-19-22-36(54)45(66-11)33(7)46(60)50-35(49(63)64)28-34-20-15-13-16-21-34)53(9)48(62)42(30(2)3)51-47(61)43(31(4)5)52(8)38(56)23-17-14-18-26-55-39(57)24-25-40(55)58/h13,15-16,20-21,24-25,30-33,35-37,42-45H,12,14,17-19,22-23,26-29H2,1-11H3,(H,50,60)(H,51,61)(H,63,64)/t32-,33+,35-,36-,37+,42-,43-,44-,45+/m0/s1

InChIKey

ORFNVPGICPYLJV-YTVPMEHESA-N

Density

1.167±0.06 g/cm3 | Condition: Temp: 20 °C Press: 760 Torr

Solubility

10 mm in DMSO

Flash Point

590.1±34.3 °C

Index Of Refraction

1.538

Vapor Pressure

0.0±0.3 mmHg at 25°C

Appearance

Soild powder

Quantity

Milligrams-Grams

Quality Standard

In-house standard

Shelf Life

2 month in rt, long time

Shipping

Room temperature, or blue ice upon request.

Storage

-20°C Freezer

Boiling Point

1052.0±65.0 °C | Condition: Press: 760 Torr

Mc-MMAF (Monomethyl Auristatin F) is a potent cytotoxic agent used primarily in the development of antibody-drug conjugates (ADCs) for targeted cancer therapies. MMAF, a microtubule-disrupting agent, is conjugated to peptides or antibodies to enable precise delivery to cancer cells. Mc-MMAF enhances the stability and solubility of MMAF, which would otherwise be too toxic and insoluble for direct therapeutic use. Its applications in ADCs aim to selectively kill tumor cells while sparing normal tissues, thus reducing systemic toxicity and improving the therapeutic index.

One of the primary applications of Mc-MMAF is in ADC formulations, which combine the specificity of monoclonal antibodies or peptides with the cytotoxicity of MMAF. The peptide or antibody part of the ADC binds specifically to cancer cell surface antigens, ensuring that the highly potent MMAF is delivered directly to the target cells. Upon internalization, MMAF disrupts microtubule dynamics, leading to cell cycle arrest and eventual cancer cell death. Mc-MMAF allows for the precise and controlled release of MMAF, minimizing damage to healthy cells and increasing the overall efficacy of the treatment.

In addition to its use in cancer therapies, Mc-MMAF plays a key role in overcoming the limitations of traditional chemotherapy. Traditional chemotherapeutic agents are often non-selective, causing widespread toxicity to both cancerous and healthy cells. Mc-MMAF, by contrast, uses the targeting power of antibodies or peptides to deliver its cytotoxic payload only to cancer cells, reducing collateral damage to normal tissues. This targeted approach makes Mc-MMAF a promising candidate for the development of more effective and less toxic cancer treatments, improving the quality of life for patients undergoing therapy.

Mc-MMAF is also instrumental in cancer research, particularly in studying drug resistance mechanisms. Many cancers develop resistance to conventional therapies by altering the microtubule network or evading apoptosis. By using Mc-MMAF conjugates in experimental models, researchers can examine how cancer cells respond to microtubule-targeting agents and identify potential mechanisms of resistance. This research is critical for the design of second-generation ADCs that can bypass common resistance pathways and provide more durable treatment responses in resistant cancer types.

Furthermore, Mc-MMAF is being explored in combination therapies to enhance its effectiveness. For instance, it can be combined with immune checkpoint inhibitors or other forms of targeted therapy to improve tumor targeting and induce synergistic effects. By using Mc-MMAF in combination with other therapeutic agents, researchers aim to create more comprehensive treatment regimens that not only target cancer cells directly but also enhance the immune response or inhibit cancer-promoting pathways. This combinatorial approach holds significant promise in improving the outcomes of cancer treatment, particularly in patients with aggressive or metastatic cancers.

1. Anti-CD22-MCC-DM1 and MC-MMAF conjugates: impact of assay format on pharmacokinetic parameters determination

Wai Lee T Wong, Christopher Nelson, Ola Saad, James Michael Elliott, Chien Lee, Jon Akutagawa, Helga Raab, Jakub Baudys, Charity Bechtel, Saileta Prabhu, David Xie, Fred Jacobson, Pamela Chan, Allen Ebens, Jean-Philippe Stephan, Richard Vandlen Bioconjug Chem . 2008 Aug;19(8):1673-83. doi: 10.1021/bc800059t.

CD22 represents a promising target for antibody-drug conjugate therapy in the context of B cell malignancies since it rapidly internalizes, importing specifically bound antibodies with it. To determine the pharmacokinetic parameters of anti-CD22-MCC-DM1 and MC-MMAF conjugates, various approaches to quantifying total and conjugated antibody were investigated. Although the total antibody assay formats gave similar results for both conjugates, the mouse pharmacokinetic profile for the anti-CD22-MCC-DM1 and MC-MMAF appeared significantly different depending on the conjugated antibody assay format. Since these differences significantly impacted the PK parameters determination, we investigated the effect of the drug/antibody ratio on the total and conjugated antibody quantification using multiple assay formats. Our investigations revealed the limitations of some assay formats to quantify anti-CD22-MCC-DM1 and MC-MMAF with different drug load and in the context of a heterogeneous ADC population highlight the need to carefully plan the assay strategy for the total and conjugated antibody quantification in order to accurately determine the ADC PK parameters.

2. Antibody-Drug Conjugates (ADCs) Derived from Interchain Cysteine Cross-Linking Demonstrate Improved Homogeneity and Other Pharmacological Properties over Conventional Heterogeneous ADCs

Jorge Monteon, Abel Bermudez, Maureen Fitch-Bruhns, Edward H Ha, Christopher R Behrens, Kristy Venstrom, Sindy Liao-Chan, Jonathan Melnick, Edward H van der Horst, Simeon Bowers, Tiffany Wong, Amanda Valdiosera, Paul Sauer, Mark R Flory, Lawrence L Chinn, Derrick Houser, Gary Probst, Thi-Sau Migone, Jan-Willem Theunissen, Zoia Levashova, David Y Jackson, Randall L Halcomb Mol Pharm . 2015 Nov 2;12(11):3986-98. doi: 10.1021/acs.molpharmaceut.5b00432.

Conventional antibody-drug conjugates (ADCs) are heterogeneous mixtures of chemically distinct molecules that vary in both drugs/antibody (DAR) and conjugation sites. Suboptimal properties of heterogeneous ADCs have led to new site-specific conjugation methods for improving ADC homogeneity. Most site-specific methods require extensive antibody engineering to identify optimal conjugation sites and introduce unique functional groups for conjugation with appropriately modified linkers. Alternative nonrecombinant methods have emerged in which bifunctional linkers are utilized to cross-link antibody interchain cysteines and afford ADCs containing four drugs/antibody. Although these methods have been shown to improve ADC homogeneity and stability in vitro, their effect on the pharmacological properties of ADCs in vivo is unknown. In order to determine the relative impact of interchain cysteine cross-linking on the therapeutic window and other properties of ADCs in vivo, we synthesized a derivative of the known ADC payload, MC-MMAF, that contains a bifunctional dibromomaleimide (DBM) linker instead of a conventional maleimide (MC) linker. The DBM-MMAF derivative was conjugated to trastuzumab and a novel anti-CD98 antibody to afford ADCs containing predominantly four drugs/antibody. The pharmacological properties of the resulting cross-linked ADCs were compared with analogous heterogeneous ADCs derived from conventional linkers. The results demonstrate that DBM linkers can be applied directly to native antibodies, without antibody engineering, to yield highly homogeneous ADCs via cysteine cross-linking. The resulting ADCs demonstrate improved pharmacokinetics, superior efficacy, and reduced toxicity in vivo compared to analogous conventional heterogeneous ADCs.

Catalog	Product Name	CAS
BADC-01432	Cys-MC-MMAF	1160590-05-5
BADC-00592	MC-Alkyl-Hydrazine Modified MMAF	1404071-64-2
BADC-01455	Modified MMAF-C5-COOH	1404071-65-3
BADC-00594	PEG4-aminooxy-MMAF	1415246-35-3
BADC-00617	MMAF sodium	1799706-65-2
BADC-01460	DBM-MMAF	1810001-93-4
BADC-00863	DBCO-PEG4-Val-Cit-PAB-MMAF	2244602-23-9
BADC-00751	DBCO-PEG4-MMAF	2360411-65-8
2413724-69-1	(R)-N-((S)-(2-(Di(adamantan-1-yl)phosphino)phenyl)(phenyl)methyl)-N,2-dimethylpropane-2-sulfinamide	2413724-69-1
389868-12-6	Ac-Glu-Glu-Val-Val-Ala-Cys-pNA	389868-12-6

What is Mc-MMAF?

Mc-MMAF is a maleimide-based linker-payload used in the development of antibody-drug conjugates (ADCs). It consists of a maleimidocaproyl (Mc) linker and a monomethyl auristatin F (MMAF) payload. This combination is designed for stable and efficient conjugation to antibodies, resulting in ADCs for targeted cancer therapy.

24/2/2020

Could you kindly advise how the Mc linker contributes to the stability of ADCs?

The Mc linker is a non-cleavable maleimide linker. It forms a stable thioether bond with the cysteine residues of the antibody. This bond is highly resistant to enzymatic cleavage in the bloodstream, which is important for preventing premature payload release and minimizing off-target toxicity.

21/7/2022

Could you kindly explain the mechanism of action of the MMAF payload?

MMAF, or monomethyl auristatin F, is a potent synthetic analog of the marine natural product dolastatin 10. It acts as a tubulin polymerization inhibitor. By binding to tubulin, MMAF disrupts the formation of microtubules, leading to cell cycle arrest at the G2/M phase and ultimately inducing apoptosis in targeted cancer cells.

8/11/2016

Why is Mc-MMAF considered a preferred choice for certain ADCs?

Mc-MMAF is often preferred for its combination of a highly stable linker and a potent payload. The non-cleavable Mc linker ensures the payload is delivered directly to the tumor cell. The MMAF payload, due to its structure, is not a substrate for P-glycoprotein efflux pumps, which can be a key factor in overcoming multi-drug resistance in some cancer cell lines.

19/9/2020

Dear team, can Mc-MMAF be used with different types of antibodies?

Yes, Mc-MMAF is a versatile linker-payload. Its maleimide group reacts with the sulfhydryl groups of reduced cysteine residues on antibodies, which can be engineered or naturally occurring. This makes it compatible with various antibody platforms, including those developed for site-specific conjugation or traditional conjugation methods.

13/8/2022

— Dr. James Parker, Senior Scientist (USA)

Mc-MMAF consistently arrived with high purity, enabling precise cytotoxicity measurements in our studies.

8/11/2016

— Dr. Olivia Harris, ADC Chemist (UK)

The batch-to-batch uniformity of Mc-MMAF ensured reproducible ADC conjugation results.

13/8/2022

— Dr. Lars Fischer, Medicinal Chemist (Germany)

Clear QC reports for Mc-MMAF helped our team avoid delays in conjugation experiments.

19/9/2020

— Dr. Emily Carter, Biochemist (Canada)

We relied on the high stability of Mc-MMAF for multi-week assays without degradation issues.