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Purity: ≥98%
Monomethyl auristatin F (also known as MMAF) is a highly potent tubulin/antimitotic inhibitor and an antineoplastic agent used as a warhead in ADCs (antibody-drug conjugates) such as vorsetuzumab mafodotin and SGN-CD19A. MMAF plus its attachment structure to the antibody are referred to as mafodotin in the International Nonproprietary Names for MMAF-antibody-conjugates. Since the N-terminal amino group of MMAF only has one methyl substituent rather than two, as it does in auristatin F itself, it is actually desmethyl-auristatin F.
| Targets |
Tubulin
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|---|---|
| ln Vitro |
MMAF prevents the growth of anaplastic large cell lymphoma. In vitro cytotoxicity assays yielded IC50 values of 119, 105, 257, and 200 nM for Karpas 299, breast carcinoma H3396, renal cell carcinoma 786-O, and Caki-1 cells[4].
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| ln Vivo |
Compared to MMAE (1 mg/kg), the mice's maximum tolerated dosage (MTD) for MMAF was significantly larger (>16 mg/kg). The equivalent cAC10-L4-MMAF4 ADC is less hazardous, with associated and related MTDs of >150 mg/kg and 90 mg/kg, respectively, compared to the 50 mg/kg MTD of cAC10-L1-MMAF4 in mice. [4].
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| Cell Assay |
Depending on the cell line, cells are treated with serial dilutions of test molecules and incubated for four to six days. The Alamar Blue dye reduction assay is used to evaluate cellular growth and reduce data in order to produce IC50 values[2].
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| Animal Protocol |
Mice: The size of the subcutaneous Karpas 299 tumor is 300 mm3, and three animals per group are given one intravenous injection of either cAC10-L1-MMAF4 or cBR96-L1-MMAF4 (10 mg antibody component/kg body weight). Immunohistochemistry evaluation is used to stain 5 μm-thin frozen tissue sections after the tumors have been removed and placed in an optimal cutting temperature compound[1].
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| References |
[1]. Lee JW, et al. EphA2 targeted chemotherapy using an antibody drug conjugate in endometrial carcinoma. Clin Cancer Res. 2010 May 1;16(9):2562-70.
[2]. Lee JJ, et al. Enzymatic prenylation and oxime ligation for the synthesis of stable and homogeneous protein-drug conjugates for targeted therapy. Angew Chem Int Ed Engl. 2015 Oct 5;54(41):12020-4. [3]. Kim EG, et al. Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted CancerTherapeutics. [4]. Doronina SO, 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 |
| Molecular Formula |
C39H65N5O8
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|---|---|
| Molecular Weight |
731.98
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| Exact Mass |
731.48331
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| Elemental Analysis |
C, 64.00; H, 8.95; N, 9.57; O, 17.49
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| CAS # |
745017-94-1
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| Related CAS # |
MMAF hydrochloride;1415246-68-2;MMAF-d8 hydrochloride;MMAF sodium;1799706-65-2;MMAF-OMe;863971-12-4;MMAF sodium;1799706-65-2;MMAF;745017-94-1;MMAF-d8
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| Appearance |
Solid powder
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| SMILES |
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC
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| InChi Key |
MFRNYXJJRJQHNW-DEMKXPNLSA-N
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| 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
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| Chemical 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
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| Synonyms |
MMAF; Monomethyl auristatin F; desmethyl-auristatin F;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product is not stable in solution, please use freshly prepared working solution for optimal results. (2). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100~140 mg/mL (136.6~191.3 mM)
Ethanol: ~100 mg/mL (~136.6 mM) Water: ~100 mg/mL (~136.6 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 3.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3662 mL | 6.8308 mL | 13.6616 mL | |
| 5 mM | 0.2732 mL | 1.3662 mL | 2.7323 mL | |
| 10 mM | 0.1366 mL | 0.6831 mL | 1.3662 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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