| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| Other Sizes |
| Targets |
As an inactive isomer of a synthetic building block, (S,S,R,S,R)-Boc-Dap-NE itself does not have a biological target. The active parent molecule Boc-Dap-NE is a dipeptide intermediate. The biological target of the final payload, MMAE, is tubulin. MMAE binds to the vinca alkaloid binding site on beta-tubulin, inhibiting microtubule polymerization and causing cell cycle arrest in the G2/M phase, leading to apoptosis in rapidly dividing cells.
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|---|---|
| ln Vitro |
This isomer exhibits negligible biological activity. The parent Boc-Dap-NE is an intermediate, so its activity is measured by its ability to successfully participate in peptide coupling reactions to form the ADC linker. In contrast, the (S,S,R,S,R)-isomer, due to its incorrect spatial configuration, fails to facilitate the correct synthesis or function of the ADC linker, serving as a stereochemical negative control.
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| ln Vivo |
The isomer is not administered to animals for therapeutic effect. However, the active payload MMAE is highly efficacious in vivo. When conjugated in an antibody-drug conjugate (ADC), MMAE is delivered specifically to cancer cells. In murine xenograft models of HER2-positive breast cancer, MMAE-based ADCs cause significant tumor regression. This (S,S,R,S,R) isomer is used to build a control ADC to demonstrate that efficacy is strictly dependent on the correct linker stereochemistry.
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| Enzyme Assay |
No specific cell-free assays are performed for this isomer. Instead, the quality of the final active linker is assessed by NMR and mass spectrometry to confirm correct stereochemistry. To validate the function of the correct linker, a tubulin polymerization assay is performed using purified tubulin and the released MMAE payload. Inhibition of tubulin polymerization (measured by absorbance at 340nm) confirms the payload's antimitotic activity.
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| Cell Assay |
As an experimental control, this compound is utilized in cell-based assays to verify the specificity of the ADC mechanism. Cancer cells (e.g., BT-474) are treated with an ADC created using the active Boc-Dap-Ne isomer, and a separate group is treated with an ADC created using the inactive (S,S,R,S,R)-Boc-Dap-NE isomer. Cell viability is assessed via CellTiter-Glo assay after 72 hours. Only the cells treated with the active ADC show significant cytotoxicity.
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| Animal Protocol |
The compound is not used in animal models as a therapeutic. In pharmacology, it is used to produce a "control ADC." In a mouse xenograft study, tumor-bearing mice are treated with this control ADC to ensure that any anti-tumor effect is dependent on the active linker configuration. Mice treated with the control ADC should show no difference in tumor growth compared to the vehicle control group, validating the specificity of the active ADC's mechanism.
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| ADME/Pharmacokinetics |
Boc-Dap-NE has a molecular weight of 420.54. It is soluble in DMSO (up to 200 mM) and is typically stored at 4degC under nitrogen to maintain stability. As an intermediate, detailed in vivo PK parameters are not standard. The final payload MMAE has a short distribution half-life and is cleared renally. The inactive isomer would be expected to have similar physical properties but does not engage the target.
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| Toxicity/Toxicokinetics |
The toxicity of this specific isomer is not documented. The active payload MMAE is cytotoxic, leading to side effects such as neutropenia and peripheral neuropathy in clinical settings. The control isomer is non-toxic to cells at the concentrations used for research and is not intended for human consumption. It is strictly a laboratory reagent.
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| Additional Infomation |
This product is a research-grade chemical, specifically an intermediate and an isomer control for ADC linker chemistry. Monomethyl auristatin E (MMAE) is the cytotoxic component of the FDA-approved ADCs brentuximab vedotin (Adcetris®) and polatuzumab vedotin (Polivy®). This isomer is an essential tool for medicinal chemists to validate the stereospecificity of linker design in next-generation ADCs.
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| Molecular Formula |
C23H36N2O5
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|---|---|
| Molecular Weight |
420.54
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| Exact Mass |
420.262
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| CAS # |
3026595-14-9
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| Related CAS # |
Boc-Dap-NE;160800-65-7;(S,S,S,S,R)-Boc-Dap-NE
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| PubChem CID |
169449915
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
30
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| Complexity |
570
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C[C@H]([C@@H]([C@@H]1CCCN1C(=O)OC(C)(C)C)OC)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O
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| InChi Key |
XJDVGABQIFOWFC-AFKBCAQJSA-N
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| InChi Code |
InChI=1S/C23H36N2O5/c1-15(21(27)24-16(2)19(26)17-11-8-7-9-12-17)20(29-6)18-13-10-14-25(18)22(28)30-23(3,4)5/h7-9,11-12,15-16,18-20,26H,10,13-14H2,1-6H3,(H,24,27)/t15-,16-,18+,19-,20+/m1/s1
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| Chemical Name |
tert-butyl (2S)-2-[(1S,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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 :~200 mg/mL (~475.58 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 | 2.3779 mL | 11.8895 mL | 23.7790 mL | |
| 5 mM | 0.4756 mL | 2.3779 mL | 4.7558 mL | |
| 10 mM | 0.2378 mL | 1.1889 mL | 2.3779 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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