| Size | Price | Stock | Qty |
|---|---|---|---|
| 50g |
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| Other Sizes |
| Targets |
Non-cleavable Linker
This compound functions as a linker molecule rather than targeting a specific biological receptor. In ADC synthesis, it serves as a non-cleavable (non-degradable) linker. Its primary role is to provide a stable covalent connection between the antibody and the cytotoxic payload, ensuring the drug is delivered specifically to the target cells. |
|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1]. Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. PROTAC selectively degrades target proteins by means of the intracellular ubiquitin-proteasome system [2].
The in vitro activity of (2R,4R)-1-tert-Butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate is realized as part of the complete ADC construct. As a non-cleavable linker, it is designed to be stable in the bloodstream and within the tumor microenvironment. The biological activity of the ADC is dependent on the target antigen and the potency of the payload. This linker allows for the release of the payload only after the ADC is internalized and the antibody is degraded in the lysosome. |
| ln Vivo |
The in vivo activity of the compound is observed through the efficacy of the ADCs it helps construct. Non-cleavable linkers like this one provide a stable linkage, which often results in a longer circulation half-life and sustained exposure of the tumor to the drug. This can lead to improved anti-tumor efficacy in preclinical xenograft models compared to cleavable linkers.
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| Enzyme Assay |
Experimental protocols for this compound focus on its use as a chemical building block. The Boc protecting group is removed under acidic conditions (e.g., TFA), and the methyl ester is hydrolyzed under basic conditions to generate the free amine and carboxylic acid for conjugation reactions. The progress of these deprotection and conjugation steps is monitored by HPLC and mass spectrometry.
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| Cell Assay |
Cell-based assays are performed using the complete ADC molecule. Target cells are treated with the ADC, and cell viability is measured using standard assays like MTT or CellTiter-Glo. The specificity of the ADC is confirmed by showing that it is only active against cells expressing the target antigen.
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| Animal Protocol |
In vivo studies are conducted in mouse xenograft models. Tumor-bearing mice are administered the ADC, and tumor growth inhibition is monitored. The non-cleavable nature of the linker often results in a favorable pharmacokinetic profile, with a prolonged half-life and reduced systemic toxicity.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of the ADC are influenced by the stability of this non-cleavable linker. It prevents premature release of the payload, contributing to a longer circulation half-life and a higher area under the curve (AUC). This allows for more efficient delivery of the drug to the tumor.
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| Toxicity/Toxicokinetics |
Toxicology studies are performed on the final ADC. The linker itself is generally considered non-toxic. The toxicity of the ADC is primarily dependent on the payload and the target. Because the linker is non-cleavable, the risk of premature payload release and associated off-target toxicity is minimized.
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| References |
[1]. Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315-337.
[2]. Nalawansha DA, et al. PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chem Biol. 2020;27(8):998-985. |
| Additional Infomation |
(2R,4R)-1-tert-Butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate is a non-cleavable ADC linker, also known as N-Boc-cis-4-hydroxy-D-proline methyl ester. It is a versatile building block used in medicinal chemistry and drug discovery, particularly for the synthesis of stable drug conjugates.
|
| Molecular Formula |
C11H19NO5
|
|---|---|
| Molecular Weight |
245.27
|
| Exact Mass |
245.126
|
| CAS # |
114676-69-6
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| PubChem CID |
6951202
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| Appearance |
White to off-white solid powder
|
| Density |
1.216g/cm3
|
| Boiling Point |
335.2ºC at 760mmHg
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| Melting Point |
80 °C
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| Flash Point |
156.6ºC
|
| Vapour Pressure |
8.47E-06mmHg at 25°C
|
| Index of Refraction |
1.5
|
| LogP |
0.467
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
|
| Heavy Atom Count |
17
|
| Complexity |
310
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
O([H])[C@@]1([H])C([H])([H])N(C(=O)OC(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])[C@@]([H])(C(=O)OC([H])([H])[H])C1([H])[H]
|
| InChi Key |
MZMNEDXVUJLQAF-HTQZYQBOSA-N
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| InChi Code |
InChI=1S/C11H19NO5/c1-11(2,3)17-10(15)12-6-7(13)5-8(12)9(14)16-4/h7-8,13H,5-6H2,1-4H3/t7-,8-/m1/s1
|
| Chemical Name |
1-O-tert-butyl 2-O-methyl (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate
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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 |
| 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) |
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
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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 | 4.0771 mL | 20.3857 mL | 40.7714 mL | |
| 5 mM | 0.8154 mL | 4.0771 mL | 8.1543 mL | |
| 10 mM | 0.4077 mL | 2.0386 mL | 4.0771 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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