| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
Auristatin E, a synthetic analog of dolastatin 10, is a novel and highly cytotoxic tubulin inhibitor with antitumor activity; it is a MMAE analog and cytotoxin used in Antibody-drug conjugates.
| Targets |
Auristatin
Monomethyl Auristatin E (MMAE) is a potent antimitotic agent that inhibits microtubule polymerization. [2] |
|---|---|
| ln Vitro |
MMAE demonstrated potent in vitro cytotoxicity against a panel of 35 non-Hodgkin lymphoma (NHL) cell lines when tested as the free drug. The sensitivity (IC50) of cell lines to free MMAE varied, but an example given is an IC50 of 0.07 nmol/L for both BJAB and WSU-DLCL2 cell lines. [2]
The in vitro potency of the antibody-drug conjugate DCDT2980S (which carries MMAE) was tested across the same NHL cell line panel. A moderate but statistically significant correlation (R² = 0.39, P < 0.0001) was found between a cell line's sensitivity to free MMAE and its sensitivity to DCDT2980S, suggesting the free drug's activity contributes to the ADC's effect. [2] |
| ln Vivo |
In SCID mouse xenograft models of anaplastic large cell lymphoma (ALCL) and Hodgkin disease (HD), cAC10-vcMMAE at 1 mg/kg induced complete and durable tumor regression. [1]
In a disseminated ALCL model, treatment with cAC10-vcMMAE starting 9 or 13 days post-tumor implantation resulted in long-term survival in 4 out of 5 mice. [1] |
| Cell Assay |
Cell Viability Assay: To determine the sensitivity of NHL cell lines to free MMAE, cells were plated in 384-well plates. MMAE was added at a series of final concentrations (200, 40, 8, 1.6, 0.32, 0.064, 0.0128, 0.0026, and 0.00051 nmol/L). After a 72-hour incubation, cell viability was measured using a luminescent cell viability assay. The concentration resulting in 50% inhibition of cell viability (IC50) was calculated from dose-response curves. [2]
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| Animal Protocol |
Xenograft Efficacy Studies: Female CB17 ICR SCID mice bearing subcutaneous NHL xenografts (e.g., BJAB, WSU-DLCL2) were used. Mice were randomized into groups when tumors reached a target volume. The antibody-drug conjugate DCDT2980S (containing MMAE) was administered as a single intravenous dose via the tail vein at specified doses (e.g., 0.1 to 16 mg/kg). Tumor volume was measured regularly, and tumor growth inhibition (TGI), partial response (PR), and complete response (CR) were calculated. Control groups received vehicle, unconjugated antibody, or a non-binding control conjugate. [2]
Pharmacokinetic Study in Mice: Female SCID mice received a single intravenous dose of DCDT2980S (0.5 or 5 mg/kg) via the tail vein. Blood samples were collected at multiple time points up to 28 days post-dose, and serum was processed for analysis of total antibody concentration. [2] Toxicity/Toxicokinetic Study in Monkeys: Cynomolgus monkeys were administered DCDT2980S intravenously every 3 weeks for a total of 5 doses at 1, 3, or 5 mg/kg. Animals underwent periodic blood collection for hematology, serum chemistry, coagulation, and toxicokinetic analysis. Physical and ophthalmologic exams were also performed. Necropsy was conducted at scheduled time points for gross and microscopic examination of tissues. [2] |
| ADME/Pharmacokinetics |
The pharmacokinetics of the conjugate DCDT2980S were investigated. In SCID mice, total antibody exposure (AUCinf) was dose-dependent after a single intravenous administration (72.1 days μg/mL at 0.5 mg/kg and 821 days μg/mL at 5 mg/kg). [2] In cynomolgus monkeys, total antibody exposure increased slightly more than dose-dependently in the 1 to 3 mg/kg dose range and increased more than dose-dependently in the 3 to 5 mg/kg dose range after multiple intravenous administrations every 3 weeks. Serum concentrations of DCDT2980S (the conjugate) decreased in a bi-exponential manner, similar to total antibody concentrations, indicating that MMAE is not rapidly released from the conjugate during circulation. Specific ADME parameters (e.g., half-life, clearance, volume of distribution) for free MMAE were not provided. [2]
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| Toxicity/Toxicokinetics |
In multiple-dose studies in cynomolgus monkeys, DCDT2980S (carrying MMAE) was well tolerated at doses up to 5 mg/kg. The main toxicity observed was reversible myelosuppression. At dose levels of 3 mg/kg and 5 mg/kg, dose-dependent reversible neutropenia and reticulopenia were observed, accompanied by a slight decrease in erythrocytes, hemoglobin, and hematocrit. Corresponding myelocytopenia was also observed. No significant cardiovascular, respiratory, renal, gastrointestinal, neurological, or ocular toxicities were observed. Specific toxicokinetic parameters or LD50 for MMAE were not provided. [2]
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| References |
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| Additional Infomation |
Monomethyl ozogatamine E (MMAE) is a microtubule disruptor used as the cytotoxic payload in the antibody-drug conjugate DCDT2980S. It is linked to an anti-CD22 antibody via a protease-cleavable linker (MC-vc-PAB). [2] Studies have shown that in vitro sensitivity to free MMAE is one factor, but not the only predictor, of cell line sensitivity to the DCDT2980S ADC. [2] The linker-drug technology (MC-vc-PAB-MMAE) used in DCDT2980S is the same as that used in the approved ADC brentuximab vedotin. [2]
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| Molecular Formula |
C40H69N5O7
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|---|---|
| Molecular Weight |
732.005171537399
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| Exact Mass |
731.519
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| Elemental Analysis |
C, 65.63; H, 9.50; N, 9.57; O, 15.30
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| CAS # |
160800-57-7
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| Related CAS # |
Auristatin E;160800-57-7
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| PubChem CID |
11498622
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| Appearance |
White to light yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
871.0±65.0 °C at 760 mmHg
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| Flash Point |
480.6±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.519
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| LogP |
4.75
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
52
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| Complexity |
1130
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| Defined Atom Stereocenter Count |
10
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| SMILES |
O(C)[C@H]([C@H](C(N[C@H](C)[C@H](C1C=CC=CC=1)O)=O)C)[C@@H]1CCCN1C(C[C@H]([C@H]([C@@H](C)CC)N(C)C([C@H](C(C)C)NC([C@H](C(C)C)N(C)C)=O)=O)OC)=O
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| InChi Key |
WOWDZACBATWTAU-FEFUEGSOSA-N
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| InChi Code |
InChI=1S/C40H69N5O7/c1-14-26(6)35(44(11)40(50)33(24(2)3)42-39(49)34(25(4)5)43(9)10)31(51-12)23-32(46)45-22-18-21-30(45)37(52-13)27(7)38(48)41-28(8)36(47)29-19-16-15-17-20-29/h15-17,19-20,24-28,30-31,33-37,47H,14,18,21-23H2,1-13H3,(H,41,48)(H,42,49)/t26-,27+,28+,30-,31+,33-,34-,35-,36+,37+/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide
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| Synonyms |
Auristatin E; synthetic analog of dolastatin 10
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| HS Tariff Code |
2934.99.03.00
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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) |
DMSO: ~100 mg/mL (~136.6 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 | 1.3661 mL | 6.8305 mL | 13.6610 mL | |
| 5 mM | 0.2732 mL | 1.3661 mL | 2.7322 mL | |
| 10 mM | 0.1366 mL | 0.6831 mL | 1.3661 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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