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| Targets |
Mc-MMAD targets tubulin, the protein that polymerizes to form microtubules, which are essential components of the cytoskeleton and play critical roles in cell division, intracellular transport, and cell shape. The MMAD payload is a potent tubulin inhibitor that binds to tubulin and prevents microtubule assembly, disrupting the mitotic spindle and causing cell cycle arrest at the G2/M phase, leading to apoptosis. The maleimidocaproyl (Mc) group provides a site for conjugation to antibodies via thiol-maleimide chemistry, enabling targeted delivery of the cytotoxic payload to cancer cells.
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| ln Vitro |
Mc-MMAD demonstrates potent in vitro activity as a tubulin inhibitor through its MMAD payload. MMAD is a potent tubulin inhibitor that inhibits cancer cell proliferation. In cell-based assays, MMAD shows potent cytotoxicity against cancer cell lines. The maleimidocaproyl (Mc) group allows for conjugation to antibodies, enabling targeted delivery of the cytotoxic payload. The compound's activity is concentration-dependent, with potent effects observed at nanomolar concentrations. Mc-MMAD is a modified peptide featuring a combination of methionine, methionine sulfoxide, and aspartic acid residues, used in biochemical and pharmaceutical research.
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| ln Vivo |
In vivo activity of Mc-MMAD is evaluated through studies of ADC constructs incorporating this payload in animal models of human cancer. The MMAD payload is a potent tubulin inhibitor that inhibits cancer cell proliferation. In tumor-bearing mouse models, ADCs containing Mc-MMAD demonstrate significant antitumor efficacy. The maleimidocaproyl (Mc) group enables conjugation to antibodies for targeted delivery. Comprehensive in vivo efficacy studies have been reported in research publications. The compound's potency and ability to inhibit tubulin polymerization make it a valuable tool for ADC development.
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| Enzyme Assay |
In vitro enzyme assays are not directly applicable to Mc-MMAD, as the compound is a tubulin inhibitor rather than an enzyme inhibitor. However, tubulin polymerization assays can be performed to characterize the compound's activity. Purified tubulin is incubated with varying concentrations of the test compound in polymerization buffer containing GTP. Tubulin polymerization is monitored by measuring the increase in absorbance at 340 nm over time using a spectrophotometer. IC50 values for inhibition of polymerization are calculated from dose-response curves. The compound's structure and purity can be characterized using analytical methods. High-performance liquid chromatography (HPLC) and mass spectrometry are used to verify the molecular weight (964.26 g/mol) and chemical composition (C51H77N7O9S). Purity (≥98%) is confirmed by HPLC analysis.
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| Cell Assay |
In vitro cellular assays for Mc-MMAD are performed using cancer cell lines. Cells are treated with varying concentrations of the compound (as an ADC or as the free payload) for 48-72 hours. Cell viability is measured using MTT or CellTiter-Glo assays. IC50 values are calculated from dose-response curves. The mechanism of cell death (apoptosis vs. necrosis) is assessed using annexin V/propidium iodide staining or caspase activity assays. Tubulin polymerization inhibition can be assessed by immunofluorescence staining of tubulin in treated cells. Cytotoxicity is compared between target antigen-positive and antigen-negative cell lines when the compound is used as an ADC. The compound is soluble in DMSO (≥100 mg/mL) and should be stored as a powder at -20degC.
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| Animal Protocol |
In vivo animal studies for Mc-MMAD are conducted using mouse xenograft models of human cancer. Immunodeficient mice are implanted subcutaneously with cancer cells expressing the target antigen. Once tumors reach a predetermined size, animals are randomized into treatment groups and administered the ADC construct via intravenous injection at various doses and schedules. Tumor size is measured twice weekly using calipers, and body weight is monitored as a safety indicator. At study termination, tumors are excised, weighed, and processed for histopathological analysis. Pharmacokinetic samples are collected to determine ADC stability and exposure. Efficacy is expressed as tumor growth inhibition (TGI) relative to vehicle control.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mc-MMAD are characterized as part of the ADC construct. The compound has a molecular formula of C51H77N7O9S and a molecular weight of 964.26 g/mol. Its chemical name is 6-(2,5-dioxopyrrol-1-yl)-N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R.... The maleimidocaproyl (Mc) group enables conjugation to antibodies via thiol-maleimide chemistry. The ADC typically exhibits biphasic elimination. The compound is soluble in DMSO (≥100 mg/mL) and should be stored as a powder at -20degC. Pharmacokinetic properties are typically assessed during ADC development.
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| Toxicity/Toxicokinetics |
Mc-MMAD is intended for laboratory research use only and has not undergone comprehensive toxicology testing. As a potent tubulin inhibitor, the compound would be expected to have significant toxicity if released systemically. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies is typically conducted as part of ADC development. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
Mc-MMAD is a protective group (maleimidocaproyl)-conjugated derivative of Monomethyl auristatin D (MMAD) for use in ADC development. MMAD is a potent tubulin inhibitor. Mc-MMAD has a molecular formula of C51H77N7O9S and a molecular weight of 964.26 g/mol. Mc-MMAD is a drug-linker conjugate for ADC. The compound has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only.
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| Molecular Formula |
C51H77N7O9S
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| Molecular Weight |
964.2636
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| Exact Mass |
963.55
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| Elemental Analysis |
C, 63.53; H, 8.05; N, 10.17; O, 14.93; S, 3.32
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| CAS # |
1401963-15-2
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| PubChem CID |
78357802
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
27
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| Heavy Atom Count |
68
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| Complexity |
1710
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| Defined Atom Stereocenter Count |
9
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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)C3=NC=CS3)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN4C(=O)C=CC4=O
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| InChi Key |
OZUQLKHIIRUJRZ-PGBUMTRMSA-N
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| InChi Code |
InChI=1S/C51H77N7O9S/c1-12-34(6)46(56(9)51(65)44(32(2)3)54-49(64)45(33(4)5)55(8)40(59)23-17-14-18-27-58-41(60)24-25-42(58)61)39(66-10)31-43(62)57-28-19-22-38(57)47(67-11)35(7)48(63)53-37(50-52-26-29-68-50)30-36-20-15-13-16-21-36/h13,15-16,20-21,24-26,29,32-35,37-39,44-47H,12,14,17-19,22-23,27-28,30-31H2,1-11H3,(H,53,63)(H,54,64)/t34-,35+,37-,38-,39+,44-,45-,46-,47+/m0/s1
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| Chemical Name |
6-(2,5-dioxopyrrol-1-yl)-N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylhexanamide
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| Synonyms |
mcMMAD; Mc-Monomethylauristatin D; maleimidocaproy Monomethylauristatin D
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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: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 mg/mL (~103.71 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.59 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 25.0 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 | 1.0371 mL | 5.1853 mL | 10.3706 mL | |
| 5 mM | 0.2074 mL | 1.0371 mL | 2.0741 mL | |
| 10 mM | 0.1037 mL | 0.5185 mL | 1.0371 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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