745017-94-1

Basic information

• Product Name: MonoMethylauristatin F
• Synonyms: MMAF;MonoMethylauristatin F;MonoMethyl Auristatin F | MMAF;MMAF (MonoMethylauristatin F);(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;(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
• CAS NO: 745017-94-1
• Molecular Formula: C₃₉H₆₅N₅O₈
• Molecular Weight: 731.96
• Mol File: 745017-94-1.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 896.8±65.0 °C(Predicted)
• Appearance: /
• Density: 1.116±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Soluble in DMSO
• PKA: 3.56±0.10(Predicted)
• CAS DataBase Reference: MonoMethylauristatin F(CAS DataBase Reference)
• NIST Chemistry Reference: MonoMethylauristatin F(745017-94-1)
• EPA Substance Registry System: MonoMethylauristatin F(745017-94-1)

Safety Data

• Hazardous Substances Data: 745017-94-1(Hazardous Substances Data)

Usage

Description

MonoMethylauristatin F (MMAF) is an effective tubulin polymerization inhibitor, derived from the auristatin family of natural products. It is characterized by a charged C-terminal phenylalanine, which differentiates it from its uncharged counterpart, Monomethyl auristatin E (MMAE). Due to its high toxicity, MMAF cannot be used as a standalone drug but instead serves as a potent cytotoxic component in antibody-conjugated drugs (ADCs), such as Vorsetuzumab mafodotin and SGN-CD19A.

Uses

Used in Anticancer Applications:
MonoMethylauristatin F is used as a cytotoxic agent for the treatment of various types of cancer. Its potent antitumor effects are achieved through conjugation with a monoclonal antibody targeting internalizing, tumor-specific cell surface antigens. The stability of the linker in extracellular fluid and its cleavage by cathepsin once inside the tumor cell activate the anti-mitotic mechanism, leading to the inhibition of tumor growth.
Used in Biotechnological Applications:
In the biotechnology industry, MonoMethylauristatin F is used as a key component in the development of antibody-conjugated drugs. Its unique properties, such as the charged C-terminal phenylalanine and high toxicity, make it an ideal candidate for creating targeted therapies with improved efficacy and reduced side effects.
Used in Drug Delivery Systems:
MonoMethylauristatin F is employed in the design and development of novel drug delivery systems, specifically for antibody-conjugated drugs. These systems aim to enhance the delivery, bioavailability, and therapeutic outcomes of MMAF by utilizing protease-cleavable linkers that ensure the drug's release only upon internalization by the target tumor cells. This targeted approach minimizes damage to healthy cells and maximizes the drug's cytotoxic effects on cancer cells.

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.

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.

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.

Upstream product

• 133645-51-9 (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3-hydroxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone 
• 180715-99-5 (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3'-methoxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone 
• 133645-49-5 (3R,4S,5S )-ethyl 4-((tert-butoxycarbonyl)amino)-3-hydroxy-5-methyl-heptanoate 
• 669074-47-9 methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-amino-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoate 
• 133565-39-6 (4S,5S)-ethyl 4-((tert-butoxycarbonyl)amino)-5-methyl-3-oxo-heptanoate 
• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 
• 149606-97-3 benzyl (2R,3R,2'S)-3-(N-tert-butoxycarbonyl-2'-pyrrolidinyl)-3-methoxy-2-methylpropanoate 
• 133565-38-5 (2R,3R)-3-[(2S)-1-[(tert-butoxy)carbonyl]pyrrolidin-2-yl]-3-hydroxy-2-methylpropanoic acid 
• 133645-50-8 (3R,4S,5S)-4-((tert-butoxycarbonyl)amino)-3-hydroxy-5-methyl-heptanoic acid 
• 159173-40-7 (2S,1'R,2'S)-N-(tert-butoxycarbonyl)-2-(1'-hydroxy-2'-methyl-3'-butenyl)-pyrrolidine 
• 159173-43-0 (2S,1'R,2'S)-N-(tert-butoxycarbonyl)-2-(1'-methoxy-2'-methyl-3'-butenyl)-pyrrolidine 
• 69610-41-9 Boc-L-Pro-H 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 

Downstream Products

• 163768-50-1 ((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutyrylamino)-N,3-dimethylbutyrylamino)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropionyl)-L-phenylalanine 
• 1415329-56-4 C₂HF₃O₂*C₅₅H₉₆N₆O₁₃ 
• 1415329-57-5 C₅₁H₈₈N₆O₁₃*ClH 
• 1415328-86-7 C₅₂H₇₉N₇O₁₁ 
• 1415329-31-5 C₄₄H₇₇N₇O₉ 

Relevant articles and documents

EFFICIENT PREPARATION OF DOLASTATIN AND AURISTATIN ANALOGS THROUGH A COMMON INTERMEDIATE

Methods for making a dolastatin, auristatin or related compounds comprising the steps of providing a universal dolastatin core of Formula (I) reacting the C-terminal carboxylic acid group with an amine (A) to form an amide bond and reacting the N-terminal amine with a carboxylic acid (CA) to form an amide bond, wherein the steps can be performed in either order. Also provided are an isolated salt of the universal dolastatin core for use in preparation of dolastatins, auristatins and related compounds. Also provided are a number of intermediates and process steps which are useful for the preparation of high purity dolastatin core and high purity dolastatin and auristatin compounds.

CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP

Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.

CONJUGATION LINKERS, CELL BINDING MOLECULE-DRUG CONJUGATES CONTAINING THE LIKERS, METHODS OF MAKING AND USES SUCH CONJUGATES WITH THE LINKERS

The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.