| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Auristatin
MMAD, the active form, targets tubulin, a critical cytoskeletal protein that polymerizes to form microtubules. By binding to tubulin, it inhibits its polymerization, leading to the disruption of the mitotic spindle and G2/M phase cell cycle arrest, which ultimately induces apoptosis in rapidly dividing cancer cells. |
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| ln Vitro |
MMAD(Monomethyl Dolastatin 10) produces a number of almost homogenous antibody-drug conjugates (ADCs) with a drug-to-antibody ratio of approximately 2.0 when coupled via a stable oxime-ligation procedure. The resultant conjugates exhibit strong in vitro cytotoxic action against HER2+ cancer cells together with good pharmacokinetic characteristics. Site-specific unnatural amino acid-based ADCs are demonstrated to have higher in vitro cytotoxicity in comparison to ADCs made by cysteine alkylation after native interchain disulfide reduction[1].
When incorporated into ADCs via a stable oxime-ligation procedure, MMAD yields conjugates with a drug-to-antibody ratio of approximately 2.0. These conjugates demonstrate potent in vitro cytotoxic activity against HER2-positive cancer cells, as well as good pharmacokinetic characteristics. Site-specific unnatural amino acid-based ADCs have shown higher in vitro cytotoxicity compared to traditional conjugates made via cysteine alkylation. |
| ln Vivo |
In rodents, the ensuing antibody-drug conjugates (ADCs) show total tumor remission. Additionally, they have a better toxicological profile in rats [1].
In rodent models, ADCs constructed with MMAD (Monomethyl Dolastatin 10) have been shown to induce total tumor remission. Furthermore, these site-specific conjugates have demonstrated a favorable toxicological profile in rats, highlighting the importance of the conjugation method for both efficacy and safety. |
| Enzyme Assay |
Not applicable. As a stable-isotope labeled internal standard, MMAD-d8 is not typically utilized as a free drug in primary binding assays. Its utility lies in the accurate quantitation of non-deuterated MMAD. Standard procedures for assessing the binding of the active MMAD payload involve using radiolabeled dolastatin 10 or its derivatives in competitive binding assays with isolated tubulin.
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| Cell Assay |
Cells are treated with serial dilutions of the ADC payload and incubated for 4-6 days. Assessment of cellular growth and IC50 determination is performed using an Alamar Blue dye reduction assay or similar cell viability methods, utilizing MMAD-d8 as an internal standard for LC-MS-based readouts in pharmacokinetic studies.
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| Animal Protocol |
For in vivo evaluation, standard protocols involve administering ADCs containing the non-deuterated MMAD payload to xenograft tumor models, typically via intravenous injection. Dosing strategies vary, but a common regimen is a single injection at a predetermined MTD or fraction thereof, with monitoring of tumor size and animal weight for signs of toxicity and efficacy.
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| ADME/Pharmacokinetics |
MMAD-d8 is intended for use as an internal standard for the quantification of MMAD by GC- or LC-MS. Its pharmacokinetic properties are expected to be nearly identical to those of the non-deuterated payload, but it is used almost exclusively in analytical settings to improve the accuracy and precision of drug quantitation in complex biological samples.
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| Toxicity/Toxicokinetics |
ADCs using the non-deuterated payload as the active cytotoxic agent have demonstrated a favorable safety profile in preclinical studies. Unconjugated or nonspecifically released payload could cause toxicity to proliferating normal tissues. The maximum tolerated dose in animal models is influenced by the conjugation site and the stability of the linker used to attach the payload to the antibody.
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| References | |
| Additional Infomation |
MMAD-d8 is a research reagent for analytical chemistry, not a therapeutic agent. Its non-deuterated parent, MMAD, is a component of many investigational ADCs. While no ADCs containing MMAD have received full FDA approval as of current knowledge, the technology platform is clinically validated, with other auristatin-based ADCs like brentuximab vedotin (MMAE) and polatuzumab vedotin (MMAE) having been approved by the FDA.
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| Molecular Formula |
C41H58D8N6O6S
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|---|---|
| Related CAS # |
MMAD;203849-91-6
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| Appearance |
Typically exists as solid at room temperature
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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 (~128.35 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.) |
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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