| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Cleavable Linker
Not applicable. This compound is a chemical linker for bioconjugation, not a drug. It has no biological target. It is a reactive reagent for forming stable, non-reducible bonds between antibodies and therapeutic payloads. The maleimide group selectively reacts with free thiols (from cysteine residues), while the NH2 group can be activated for acylation reactions to attach to carboxylic acid-containing payloads or further crosslinkers. |
|---|---|
| ln Vitro |
An ADC cytotoxin is connected to an antibody by use of an ADC linker to form an ADC.
No significant direct in vitro activity reported. The compound is a biologically inert chemical reagent. Its value is in enabling the synthesis of stable ADCs. The resulting ADCs can demonstrate highly potent and specific in vitro cytotoxicity against target-positive cancer cells. The non-cleavable nature of the linker means the ADC retains the payload until the entire antibody is degraded inside the lysosome. |
| ln Vivo |
No specific in vivo data reported. As a linker, it is not studied directly in vivo. However, ADCs synthesized with this non-cleavable linker have demonstrated efficacy in tumor xenograft models. The MC-PEG2-NH2 linker provides high stability in circulation, which can reduce off-target toxicity. The linker's non-cleavable nature leads to a longer circulation time and a distinct toxicity profile compared to cleavable linkers.
|
| Enzyme Assay |
Not applicable. This is a chemical reagent for bioconjugation. A typical conjugation protocol involves first reducing the interchain disulfide bonds of a monoclonal antibody (mAb) with TCEP (tris(2-carboxyethyl)phosphine) to generate free thiols. MC-PEG2-NH2 is first conjugated to a drug payload (e.g., a carboxylic acid-containing toxin) via an amide bond using EDC/HOBT chemistry to form a drug-linker. This drug-linker is then added to the reduced mAb at a 1:10 to 1:20 molar ratio and incubated for 1-2 hours at room temperature. Unreacted maleimide is quenched with N-acetyl cysteine (NAC).
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| Cell Assay |
Not applicable. The compound itself is not used in cell-based assays. The final ADC produced with this linker is used for testing. The target-positive cancer cell line and a control target-negative cell line are seeded in 96-well plates (5,000 cells/well). Cells are treated with serial dilutions of the ADC (1 pM to 100 nM) for 72-120 hours. Cell viability is measured using the CellTiter-Glo (ATP) assay. A selectivity window between the target-positive and target-negative cell lines indicates successful ADC function. The non-cleavable linker typically leads to a slower onset of cytotoxicity in vitro.
|
| Animal Protocol |
No specific in vivo animal study protocols are documented for the linker itself. For an ADC synthesized with MC-PEG2-NH2, a typical protocol would involve establishing subcutaneous xenografts of a target-positive cancer cell line in 6-8 week old female NSG mice. When tumors reach ~200 mm3, mice are treated with a single intravenous (i.v.) dose or weekly doses of the ADC for 2-3 cycles (e.g., 3 mg/kg). The primary endpoint is tumor growth inhibition (TGI). The secondary endpoint is safety, assessed by body weight loss and serum chemistry, as non-cleavable linkers can cause different on-target/off-tumor toxicities.
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| ADME/Pharmacokinetics |
Not applicable for the linker. The non-cleavable maleimide-PEG2-NH2 linker is designed for high stability. The maleimide linkage to the antibody thiol is reversible but is considered stable in circulation. The PEG2 spacer improves water solubility and reduces aggregation. ADCs made with this linker have a pharmacokinetic profile similar to the unconjugated antibody, with a half-life of several days to weeks, depending on the antibody.
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| Toxicity/Toxicokinetics |
No toxicity data reported. MC-PEG2-NH2 is a chemical reagent. Standard chemical safety precautions apply. The maleimide group is an irritant and potential sensitizer; avoid skin contact. The linker itself has low systemic toxicity, but the final ADC is highly potent. For ADCs, non-cleavable linkers such as this one are associated with a specific type of off-target toxicity known as "bystander effect" because the active payload is not released from the dying target cell to kill neighboring antigen-negative tumor cells.
|
| References |
[1]. Hans-Georg Lerchen, et al. Prodrugs of cytotoxic active agents having enzymatically cleavable groups. US20190077752A1.
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| Additional Infomation |
This is a non-cleavable ADC linker. The maleimide (MC) group is reactive with thiols. The PEG2 spacer has the exact formula of -O-CH2-CH2-O-CH2-CH2-, which increases hydrophilicity and reduces aggregation. This linker is used to create stable, non-reducible ADCs. The final conjugate is not cleaved in the blood, and the cytotoxic drug is only released after the entire antibody moiety is degraded inside the lysosome of the target cell. It is for research use only. Not for therapeutic use. Molecular formula: C16H27N3O5; molecular weight: 341.40.
|
| Molecular Formula |
C16H27N3O5
|
|---|---|
| Molecular Weight |
341.40
|
| Exact Mass |
341.195
|
| CAS # |
640267-62-5
|
| PubChem CID |
121412773
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
-0.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
14
|
| Heavy Atom Count |
24
|
| Complexity |
421
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1(CCCCCC(NCCOCCOCCN)=O)C(=O)C=CC1=O
|
| InChi Key |
BRPNMDKROWMZAK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H27N3O5/c17-7-10-23-12-13-24-11-8-18-14(20)4-2-1-3-9-19-15(21)5-6-16(19)22/h5-6H,1-4,7-13,17H2,(H,18,20)
|
| Chemical Name |
N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-6-(2,5-dioxopyrrol-1-yl)hexanamide
|
| 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 and light. |
| 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
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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 | 2.9291 mL | 14.6456 mL | 29.2912 mL | |
| 5 mM | 0.5858 mL | 2.9291 mL | 5.8582 mL | |
| 10 mM | 0.2929 mL | 1.4646 mL | 2.9291 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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