| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
The intermediate itself has no direct biological target. MMAE, the final API for which this intermediate is used, binds to the vinca domain on tubulin, preventing microtubule polymerization and leading to G2/M phase cell cycle arrest and apoptotic cell death in rapidly dividing cells.
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|---|---|
| ln Vitro |
Monomethyl auristatin E intermediate-9 has no direct in vitro activity. However, MMAE exhibits potent in vitro cytotoxic activity against a wide range of cancer cell lines, including NCI-H460 (IC50 ≈ 0.1 nM), HCT-116 (IC50 ≈ 0.3 nM), HL-60 (IC50 ≈ 0.5 nM), and MCF-7 (IC50 ≈ 0.8 nM).
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| ln Vivo |
The intermediate itself has no direct in vivo activity. MMAE, when conjugated as the payload in ADCs, demonstrates potent antitumor efficacy in xenograft models at doses of 0.1-3 mg/kg (IV). The unconjugated toxin has a short circulation time and significant toxicity. Conjugation to antibodies improves targeting and tolerability.
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| Enzyme Assay |
As a chemical intermediate, Monomethyl auristatin E intermediate-9 is not used in biological assays. For quality control, HPLC (≥98% purity) and LC-MS are used to confirm its molecular weight (393.52 g/mol) and molecular formula (C22H35NO5). NMR spectroscopy is used for structural verification and purity assessment.
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| Cell Assay |
Cell-based assays are not performed directly on this intermediate. For MMAE, typical protocols involve seeding cancer cells (5000 cells/well) in 96-well plates overnight, treating with serial dilutions of MMAE (0.001 nM to 100 nM) for 48-96 hours, and measuring viability with MTT, CellTiter-Glo, or assessing apoptosis by Annexin V/PI staining.
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| Animal Protocol |
Animal studies are not conducted directly on this intermediate. For MMAE-based ADCs, typical protocols involve subcutaneous implantation of tumor cells into immunocompromised mice. When tumors reach ~100-200 mm3, the ADC (0.5-5 mg/kg) or unconjugated MMAE (0.01-0.1 mg/kg) is administered intravenously once or twice weekly, with tumor volume monitored.
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| ADME/Pharmacokinetics |
No pharmacokinetic data is available for this intermediate. For MMAE, unconjugated PK shows a short half-life (t1/2 ≈ 15-30 minutes) in rodents, high plasma protein binding (>90%), and rapid clearance. When conjugated to an antibody, the ADC exhibits a prolonged half-life (3-7 days) due to decreased renal clearance and antibody recycling.
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| Toxicity/Toxicokinetics |
No direct toxicity data is available for this intermediate. MMAE is highly potent and toxic; it can cause dose-limiting neutropenia, peripheral neuropathy, gastrointestinal toxicity, and liver enzyme elevations. Appropriate safety precautions and personal protective equipment must be used when handling intermediate-9.
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| References | |
| Additional Infomation |
Monomethyl auristatin E intermediate-9 is a research-use chemical and not a pharmaceutical for human consumption. MMAE acts as a tubulin polymerization inhibitor and is a key component of several FDA-approved ADCs, including Brentuximab vedotin (Adcetris) and Polatuzumab vedotin (Polivy). This intermediate is for research use only and is not intended for therapeutic applications.
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| Molecular Formula |
C22H35NO5
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|---|---|
| Molecular Weight |
393.52
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| Exact Mass |
393.251
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| CAS # |
120205-58-5
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| Related CAS # |
Monomethyl auristatin E intermediate-10
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| PubChem CID |
10249994
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| Appearance |
Colorless to light yellow ointment
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
28
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| Complexity |
482
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC[C@H](C)[C@@H]([C@@H](CC(=O)OC(C)(C)C)OC)N(C)C(=O)OCC1=CC=CC=C1
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| InChi Key |
PCUHBNWYHLQSBO-HQRMLTQVSA-N
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| InChi Code |
InChI=1S/C22H35NO5/c1-8-16(2)20(18(26-7)14-19(24)28-22(3,4)5)23(6)21(25)27-15-17-12-10-9-11-13-17/h9-13,16,18,20H,8,14-15H2,1-7H3/t16-,18+,20-/m0/s1
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| Chemical Name |
tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(phenylmethoxycarbonyl)amino]heptanoate
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.5412 mL | 12.7058 mL | 25.4117 mL | |
| 5 mM | 0.5082 mL | 2.5412 mL | 5.0823 mL | |
| 10 mM | 0.2541 mL | 1.2706 mL | 2.5412 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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