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| 1mg |
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D8-MMAE is the deuterated form of MMAE, which is a naturally occurring and highly potent mitotic inhibitor with strong antitumor activities, often used a cytotoxic warhead for ADCs.
| Targets |
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| ln Vitro |
Targeting antibodies with strong small-molecule payloads are combined to form antibody-drug conjugates (ADC). On the anaplastic large cell lymphoma line L-82, ADCs are designed to target distinct receptors. However, they all deliver the same cytotoxic payload, monomethyl auristatin E, or MMAE. Independent of target expression or drug:antibody ratios, the intracellular concentration of released MMAE correlated with in vitro ADC-mediated cytotoxicity. Using a parallel cohort of L-82 tumors under the same treatment protocol, the concentration of MMAE is measured by LC-MS. Two patterns are seen in the intratumoral MMAE measurement three days after dosage, despite the fact that tumor volume is not varied between treatment groups. In order to achieve more anticancer effect, the intratumoral MMAE concentration first rises in direct proportion to the ADC dose. Furthermore, it was observed that the tumor responded equally to both ADCs[1] and that the intratumoral MMAE concentration derived from Treatment with both cOKT9-vcMMAE and cAC10-vcMMAE is similar at each dose.
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| ln Vivo |
In tumor xenograft models, intramoral MMAE concentrations are reliably correlated with the degree of tumor growth inhibition. Because nonbinding control treatments do not kill either CD30+ or CD30-Karpas 299 cells, IHC analysis shows that tumors treated with these treatments contain both CD30+ and CD30- cells. Tumors treated with cAC10-vcMMAF only contain CD30- cells, indicating that the majority of CD30+ cells are eliminated by cAC10-vcMMAF. It's interesting to note that by the time the study is over, both of the tumors that relapsed after receiving cAC10-vcMMAE treatment were also discovered to be CD30-, suggesting that some CD30- cells may have managed to elude bystander death in these two surviving tumors[1].
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| References |
| Molecular Formula |
C39H67N5O7
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|---|---|
| Molecular Weight |
726.0279
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| Exact Mass |
725.554
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| CAS # |
2070009-72-0
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| Related CAS # |
Monomethyl auristatin E;474645-27-7
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| PubChem CID |
78357789
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
51
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| Complexity |
1100
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| Defined Atom Stereocenter Count |
10
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| SMILES |
O(C([H])([H])[H])[C@]([H])([C@]([H])(C(N([H])[C@]([H])(C([H])([H])[H])[C@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])O[H])=O)C([H])([H])[H])[C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])([H])[C@]([H])([C@]([H])([C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])N(C([H])([H])[H])C([C@]([2H])(C([2H])(C([2H])([2H])[2H])C([2H])([2H])[2H])N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([H])([H])[H])=O)=O)OC([H])([H])[H])=O
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| InChi Key |
DASWEROEPLKSEI-CMHCZSPYSA-N
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| InChi Code |
InChI=1S/C39H67N5O7/c1-13-25(6)34(43(10)39(49)33(24(4)5)42-38(48)32(40-9)23(2)3)30(50-11)22-31(45)44-21-17-20-29(44)36(51-12)26(7)37(47)41-27(8)35(46)28-18-15-14-16-19-28/h14-16,18-19,23-27,29-30,32-36,40,46H,13,17,20-22H2,1-12H3,(H,41,47)(H,42,48)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1/i4D3,5D3,24D,33D
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| Chemical Name |
(2S)-2,3,4,4,4-pentadeuterio-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-methyl-2-[[(2S)-3-methyl-2-(methylamino)butanoyl]amino]-3-(trideuteriomethyl)butanamide
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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 (~137.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.44 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 (3.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3774 mL | 6.8868 mL | 13.7735 mL | |
| 5 mM | 0.2755 mL | 1.3774 mL | 2.7547 mL | |
| 10 mM | 0.1377 mL | 0.6887 mL | 1.3774 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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