| Identification | Back Directory | [Name]
MonoMethylauristatin F | [CAS]
745017-94-1 | [Synonyms]
MMAF
F(MMAF)
Tacrinum
745017-97-1
Methyloratatin F
MonoMethylauristatin
MonoMethylauristatin F
Thiazole,2-bromo-6-methyl-
MMAF
(MonoMethylauristatin F)
MonoMethyl Auristatin F | MMAF
745017-94-1 MonoMethylauristatin F
Monomethyl auristatin phenylalanine
MMAF (Synonyms: Monomethylauristatin F)
MONOMETHYLAURISTATIN F; MMAF; MONOMETHYL AURISTATIN PHENYLALANINE; 745017-94-1
L-Phenylalanine, 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-
(S)-2-((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-methylpropanamido)-3-phenylpropanoic acid
(2S)-2-[[(2R,3R)-3-methoxy-3-[(2S)-1-[(3R,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
(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
(S)-2-((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-methylpropanamido)-3-phenylpropanoic acid[Monomethylauristatin F | [Molecular Formula]
C39H65N5O8 | [MDL Number]
MFCD25976742 | [MOL File]
745017-94-1.mol | [Molecular Weight]
731.96 |
| Chemical Properties | Back Directory | [Boiling point ]
896.8±65.0 °C(Predicted) | [density ]
1.116±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,Room Temperature | [solubility ]
Soluble in DMSO | [form ]
A solid | [pka]
3.56±0.10(Predicted) | [color ]
White to off-white | [Stability:]
Hygroscopic | [InChIKey]
MFRNYXJJRJQHNW-UQVYMQKONA-N |
| Hazard Information | Back Directory | [Description]
MMAF (Monomethylauristatin F) is an effective tubulin polymerization inhibitor, used as an anti-tumor drug. MMAF (Monomethylauristatin F) is widely used as the cytotoxic component of antibody-conjugated drugs (ADCs), such as Vorsetuzumab mafodotin and SGN-CD19A. | [Uses]
Monomethyl Auristatin F is an antimicrotubule agent. A potent mitotic inhibitor. | [Biological Activity]
MMAF (Monomethylauristatin F) is a potent tubulin polymerization inhibitor and is used as a antitumor agent. MMAF (Monomethylauristatin F) is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) such as vorsetuzumab mafodotin and SGN-CD19A. | [Biotechnological Applications]
MMAF is a new auristatin derivative with a charged C-terminal phenylalanine that attenuates its cytotoxic activity compared to its uncharged counterpart, Monomethyl auristatin E (MMAE). 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. | [Synthesis]
The synthesis of (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-N,3-dimethyl-2-((S)-3-methyl-2-(methylaminopropionamido)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl) was carried out using the compound (CAS: 1369427-27-9) as starting material. (methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoic acid was prepared in the following general steps: (S)-2-((2R,3R)-3-((S)-1-((6S,9S,12S,13R)-12-((S)-sec-butyl)-6,9-diisopropyl-13-methoxy-2,2,5,11-tetramethyl-4,7,10-trioxo-3- oxa-5,8,11-triazatetradecan-15-yl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoic acid (25 mg, 0.030 mmol) was dissolved in a mixture of 0.3 ml of HCl and 0.9 ml of 1,4-dioxane and stirred at room temperature for 35 min. The reaction mixture was diluted with 1.0 ml of ethanol and 1.0 ml of toluene, subsequently concentrated and evaporated again with ethanol/toluene (2:1) to afford the target product (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butyramido)butanamide (S)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoic acid as a white solid (22 mg, about 400% yield), which can be used in the next reaction without further purification.LC-MS (ESI) m/z calculated value: C39H66N5O8 [M + H]+: 732.48, measured value: 732.60. | [in vitro]
MMAF inhibits anaplastic large cell lymphoma Karpas 299, breast carcinoma H3396, renal cell carcinoma 786-O and Caki-1 cells with IC50s of 119, 105, 257 and 200 nM in vitro cytotoxicity assay. | [References]
[1] Patent: WO2015/155753, 2015, A2. Location in patent: Page/Page column 101
[2] Patent: WO2018/86139, 2018, A1. Location in patent: Page/Page column 192; 193
[3] Patent: WO2012/166560, 2012, A1. Location in patent: Page/Page column 165
[4] Patent: WO2013/185117, 2013, A1. Location in patent: Paragraph 00453
[5] Patent: WO2016/59622, 2016, A2. Location in patent: Page/Page column 130 |
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