| Size | Price | |
|---|---|---|
| 50mg | ||
| Other Sizes |
| Targets |
The compound itself, as an inactive isomer, does not have a direct biological target. However, the parent molecule Boc-Dap-NE is a synthetic building block for MMAE. The active target of the final payload MMAE is tubulin. Specifically, MMAE binds to the vinca alkaloid binding site on beta-tubulin, inhibiting tubulin polymerization. This disrupts the mitotic spindle during cell division, leading to G2/M cell cycle arrest and eventual apoptosis in dividing cells.
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| ln Vitro |
(S,S,S,S,R)-Boc-Dap-NE is the designated inactive isomer and as such, it exhibits negligible activity in cellular and biochemical assays. The active isomer of Boc-Dap-NE or the final MMAE payload is responsible for the antimitotic activity. As an experimental control, this isomer is used to demonstrate that biological effects observed in ADC studies are stereospecific and mediated by the intended target, not by off-target interactions of the intermediate.
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| ln Vivo |
There is no in vivo activity for this specific inactive isomer. The active parent MMAE, when conjugated in an antibody-drug conjugate (ADC), demonstrates potent anti-tumor activity in xenograft mouse models. Upon ADC internalization and catabolism, the active payload is released, causing tumor regression. This inactive isomer serves as a negative control in such animal studies to validate that the observed anti-cancer efficacy is dependent on the correct stereochemistry.
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| Enzyme Assay |
No specific cell-free assays are performed for this isomer. Typically, the biological activity is validated by studying the binding of the active MMAE payload to tubulin. In a standard tubulin polymerization assay, purified tubulin (from bovine brain) is incubated with GTP at 37degC and varying concentrations of the active compound. The polymerization is monitored spectrophotometrically at 340 nm. An increase in absorbance indicates microtubule formation, while inhibition indicates binding.
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| Cell Assay |
For an inactive isomer like this, its utility lies in cell viability assays as a negative control. In a typical ADC development workflow, cancer cells (e.g., HER2-positive BT-474 cells) are treated with serial dilutions of an ADC. Parallel experiments are run using an ADC synthesized with the inactive isomer (S,S,S,S,R)-Boc-Dap-NE as a negative control. Cell viability is measured after 72-96 hours using a luminescent CellTiter-Glo assay. The active ADC will show potent cytotoxicity (nM IC50), while the control ADC will show no effect.
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| Animal Protocol |
The (S,S,S,S,R)-Boc-Dap-NE isomer is not intended for administration in animal models. Instead, it is used as a control reagent for in vivo studies of ADC efficacy. For example, in a mouse xenograft model, one group of tumor-bearing mice is treated with the active ADC, while a second control group is treated with an ADC built using the inactive Boc-Dap-NE isomer. This validates that tumor growth inhibition is target-specific and not caused by non-specific linker-payload toxicity.
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| ADME/Pharmacokinetics |
Boc-Dap-Ne derivatives (MW 420.54) are generally stored at 4degC, under nitrogen, and are soluble in DMSO (up to 200 mg/mL). As an intermediate, it is not evaluated for pharmacokinetic properties in vivo. However, when MMAE is released from an ADC in vivo, the active payload has a short plasma half-life due to rapid tissue distribution and clearance. The inactive isomer would be expected to have similar PK properties but without target engagement.
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| Toxicity/Toxicokinetics |
The toxicity of (S,S,S,S,R)-Boc-Dap-NE itself is not characterized. The active payload MMAE is highly cytotoxic and is classified as an ADC cytotoxin. In clinical ADC applications, common toxicities associated with MMAE payloads include neutropenia, peripheral neuropathy, and fatigue. The inactive isomer is non-toxic to cells at the concentrations used for control experiments and is not intended for therapeutic use.
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| Additional Infomation |
(S,S,S,S,R)-Boc-Dap-NE is a research-grade chemical used exclusively as an analytical reference and experimental control in the development of antibody-drug conjugates (ADCs). MMAE is a clinically validated payload used in FDA-approved ADCs such as brentuximab vedotin (Adcetris®) for Hodgkin lymphoma and enfortumab vedotin (Padcev®) for urothelial cancer. This product is for research use only and is not FDA-approved for human therapy.
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| Molecular Formula |
C23H36N2O5
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|---|---|
| Molecular Weight |
420.54
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| Related CAS # |
Boc-Dap-NE;160800-65-7;(S,S,R,S,R)-Boc-Dap-NE
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| Appearance |
White to off-white solid powder
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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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