MMAF
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| Category | Mycotoxins |
| Catalog number | BBF-05779 |
| CAS | 745017-94-1 |
| Molecular Weight | 731.48 |
| Molecular Formula | C39H65N5O8 |
| Purity | ≥98% by HPLC |
Ordering Information
| Catalog Number | Size | Price | Stock | Quantity |
|---|---|---|---|---|
| BBF-05779 | 10 mg | $358 | In stock |
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Monomethyl auristatin F (MMAF) is a synthetic antineoplastic agent. 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.
Specification
| Related CAS | 1415246-68-2 (hydrochloride) |
| 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 |
| Shelf Life | ≥12 months if stored properly |
| Storage | Store at 2-8°C under inert atmosphere |
| 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 |
| InChI Key | MFRNYXJJRJQHNW-DEMKXPNLSA-N |
Properties
| Appearance | White to Off-white Solid |
| Application | ADCs Cytotoxin |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Boiling Point | 896.8±65.0 °C at 760 mmHg |
| Melting Point | >137°C (dec.) |
| Flash Point | 496.2±34.3 °C |
| Density | 1.116±0.06 g/cm3 (Predicted) |
| Solubility | Soluble in DMF (Slightly), DMSO (Slightly), Methanol (Slightly), Water (Slightly) |
| LogP | 4.36 |
Reference Reading
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.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
