| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| Other Sizes |
| Targets |
As the inactive isomer, (R,S,S,R,S)-Boc-Dap-NE does not have a traditional biological target but is used as a negative control. The parent compound Boc-Dap-NE is an intermediate for MMAE, which targets tubulin. MMAE binds to the vinca alkaloid binding site on beta-tubulin, inhibiting tubulin polymerization, disrupting microtubule dynamics, and causing G2/M cell cycle arrest and apoptosis.
|
|---|---|
| ln Vitro |
As a non-active isomer, (R,S,S,R,S)-Boc-Dap-NE shows no direct biological activity. The active parent compound MMAE (Monomethyl auristatin E) inhibits tubulin polymerization with IC50 values in the low nanomolar range. MMAE causes mitotic block and cell death in various cancer cell lines with sub-nanomolar to low nanomolar cytotoxic potencies. This inactive isomer serves as a negative control to validate target-specific effects.
|
| ln Vivo |
No in vivo activity data is available for (R,S,S,R,S)-Boc-Dap-NE itself. The active payload MMAE demonstrates potent antitumor activity in xenograft mouse models, and ADCs utilizing MMAE have shown significant tumor growth inhibition in multiple preclinical models, leading to FDA approval for clinical use in hematologic malignancies like Hodgkin lymphoma and anaplastic large cell lymphoma.
|
| Enzyme Assay |
The parent active compound Boc-Dap-NE is used in peptide coupling reactions for MMAE synthesis. For tubulin polymerization assays, purified tubulin is incubated with GTP and varying concentrations of test compound at 37degC. Polymerization is monitored spectrophotometrically at 340 nm for 30-60 minutes. MMAE inhibits polymerization with IC50 values of 1-5 nM. For binding studies, [3H]-vincristine is used to competitively displace MMAE from tubulin.
|
| Cell Assay |
Cell viability assays are performed in 96-well plates using various cancer cell lines (e.g., HeLa, A549, MCF-7, HCT116, HL-60). Cells are treated with serial dilutions of active MMAE or the inactive isomer as control for 48-96 hours. Cell viability is measured using MTT, CCK-8, or CellTiter-Glo assays. IC50 values for MMAE typically range from 0.1-10 nM depending on cell line, while the inactive isomer shows no cytotoxicity.
|
| Animal Protocol |
For the parent active compound MMAE, in vivo efficacy is evaluated in subcutaneous xenograft models. Immunodeficient mice bearing established tumors (e.g., xenografted human lymphoma or carcinoma cells) are treated intravenously with MMAE (1-5 mg/kg) on a Q4D x 3 schedule. Tumor volumes are measured by calipers twice weekly, and body weight is monitored for toxicity. MMAE typically produces tumor growth inhibition (TGI) >80% or frank regression at efficacious doses.
|
| ADME/Pharmacokinetics |
As an inactive isomer, pharmacokinetic data for (R,S,S,R,S)-Boc-Dap-NE is not publicly available. For the parent MMAE, typical PK parameters in rodents include moderate plasma clearance (CL = 10-30 mL/min/kg), moderate volume of distribution (Vd = 1-3 L/kg), and terminal half-life (t1/2 = 2-6 hours). As a peptide-based toxin, MMAE has low oral bioavailability and is typically administered intravenously. It is primarily metabolized by CYP3A4 in the liver.
|
| Toxicity/Toxicokinetics |
The inactive isomer is non-toxic at the concentrations used for control experiments. For the active parent compounds Boc-Dap-NE and MMAE, toxicology studies have been conducted as part of ADC development. MMAE-related toxicities include bone marrow suppression (neutropenia, thrombocytopenia), peripheral neuropathy, and gastrointestinal effects. The inactive isomer is not intended for therapeutic use and no systematic toxicology data is available.
|
| References | |
| Additional Infomation |
(R,S,S,R,S)-Boc-Dap-NE is a research-grade chemical used exclusively as a negative control in ADC drug development. Boc-Dap-NE (as an intermediate) and MMAE (as the active payload) are critical components of FDA-approved ADCs, including brentuximab vedotin (Adcetris®), which was first approved in 2011 for Hodgkin lymphoma and anaplastic large cell lymphoma. The inactive isomer helps validate target-specific effects in research settings.
|
| Molecular Formula |
C23H36N2O5
|
|---|---|
| Molecular Weight |
420.54
|
| Exact Mass |
420.262
|
| CAS # |
2994330-72-0
|
| Related CAS # |
Boc-Dap-NE;160800-65-7
|
| PubChem CID |
138958211
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
30
|
| Complexity |
570
|
| Defined Atom Stereocenter Count |
5
|
| 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
|
| InChi Key |
XJDVGABQIFOWFC-LERVOYGESA-N
|
| 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-/m0/s1
|
| Chemical Name |
tert-butyl (2R)-2-[(1S,2S)-3-[[(1R,2S)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
