| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Auristatin
MMAF-d8 targets tubulin, a key structural protein in eukaryotic cells. By binding to tubulin, it disrupts the formation of microtubules, which is essential for mitosis. This leads to mitotic arrest and apoptosis in rapidly dividing cells, a mechanism that is particularly leveraged in oncology for targeted cancer therapies. |
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| ln Vitro |
MMAF demonstrates cytotoxicity in vitro towards a range of cell lines. Karpas 299, H3396, 786-O, and Caki-1 have IC50 values of 119, 105, 257, and 200 nM, in that order. Targeted MMAF exhibits notable activity through cAC10 conjugates, and it is far more potent than the free drug. The cAC10-L1-MMAF4 is active on all examined CD30-positive cell lines and has an average potency of about 2200 times that of free MMAF on a molar basis[1].
MMAF demonstrates potent in vitro cytotoxicity against a wide range of cancer cell lines. The IC₅0 values for Karpas 299, H3396, 786-O, and Caki-1 cell lines are 119, 105, 257, and 200 nM, respectively. When conjugated to an antibody (cAC10-L1-MMAF4), it shows an average potency over 2200-fold greater than free MMAF against CD30-positive cell lines on a molar basis. |
| ln Vivo |
MMAF has a substantially larger maximum tolerated dose in mice (>16 mg/kg) than MMAE (1 mg/kg). The MTD of cAC10-L1-MMAF4 is 15 mg/kg in rats and 50 mg/kg in mice. With MTDs in mice and rats of >150 mg/kg and 90 mg/kg in rats, respectively, the comparable cAC10-L4-MMAF4 ADC was significantly less toxic[1].
MMAF as a free drug has a maximum tolerated dose in mice exceeding 16 mg/kg, which is considerably higher than that of MMAE (1 mg/kg). The ADC cAC10-L1-MMAF4 has a MTD of 50 mg/kg in mice and 15 mg/kg in rats, demonstrating a significantly better safety profile than its non-cleavable counterpart, which allows for a larger therapeutic window. |
| Enzyme Assay |
Not applicable. As a deuterated internal standard, it is not used in primary enzyme/receptor assays. The non-deuterated form, MMAF, is a well-characterized tubulin polymerization inhibitor whose activity is typically measured in a tubulin polymerization assay. A standard protocol for assessing tubulin binding involves incubating purified tubulin with the compound and measuring the turbidity (absorbance at 340 nm) over time. The generic term "MethADP" in prior descriptions was a search error; the correct target is tubulin.
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| Cell Assay |
The standard protocol for assessing the cytotoxicity of MMAF-d8 or its conjugates is an Alamar Blue or MTT viability assay. In this protocol, cells are treated with serial dilutions of the test molecule and incubated for 4-6 days, after which cell viability is assessed to generate IC₅0 values.
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| Animal Protocol |
For in vivo assessment of MMAF-d8 containing ADCs, standard protocols involve administering the ADC to xenograft tumor models via intravenous injection. Dosing frequency and duration vary, but a typical protocol might involve a single injection at doses near the MTD. Tumor size is measured every 2-3 days to assess efficacy (tumor growth inhibition), and animal body weight is monitored for signs of toxicity.
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| ADME/Pharmacokinetics |
MMAF-d8 is a stable isotope-labeled compound that is indistinguishable from its non-deuterated counterpart in vivo, but the introduction of deuterium can potentially alter metabolic stability. It is primarily intended for use as an internal standard in LC-MS assays to accurately quantify levels of MMAF and its conjugates in biological matrices, such as plasma or tumor homogenates.
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| Toxicity/Toxicokinetics |
As an experimental payload for ADCs, toxicity is largely determined by its linkage and targeting. Off-target toxicity includes the inhibition of tubulin polymerization in normal, rapidly dividing cells. The MTD of the free drug in mice (>16 mg/kg) indicates a manageable safety profile when the payload is not targeted but serves as a benchmark for ADC safety evaluations.
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| References | |
| Additional Infomation |
MMAF-d8 hydrochloride is an isotopically labeled research compound used exclusively for drug quantitation and metabolism studies. It is a derivative of MMAF, which is a high-affinity payload used in antibody-drug conjugates (ADCs) like those based on the cAC10 antibody. It is not an approved drug itself but serves as a crucial reagent in the development and analysis of advanced cancer therapies. It is strictly for laboratory research use and not for human therapeutic applications.
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| Molecular Formula |
C39H58D8CLN5O8
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|---|---|
| Molecular Weight |
776.47
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| Related CAS # |
MMAF;745017-94-1;MMAF hydrochloride;1415246-68-2;MMAF sodium;1799706-65-2;MMAF-d8
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| Appearance |
White to off-white solid powder
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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 mg/mL (~128.79 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2879 mL | 6.4394 mL | 12.8788 mL | |
| 5 mM | 0.2576 mL | 1.2879 mL | 2.5758 mL | |
| 10 mM | 0.1288 mL | 0.6439 mL | 1.2879 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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