| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Non-cleavable Linker
The primary targets of Mal-Ph-CONH-PEG4-NHS ester are the linker structures in ADC technology. As a non-cleavable ADC linker, it connects the antibody to the cytotoxic payload, providing stability to the conjugate. The maleimide group reacts with thiol groups on antibodies or payloads, while the NHS ester reacts with primary amines. The PEG4 spacer enhances solubility and reduces aggregation of the conjugate. The compound does not directly bind to enzymes or receptors but serves as a structural component. |
|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
In vitro, Mal-Ph-CONH-PEG4-NHS ester functions as a structural linker for ADC synthesis. The maleimide group selectively reacts with thiols, and the NHS ester couples efficiently with primary amines. The PEG4 spacer provides water solubility and flexibility to the conjugate. The non-cleavable nature ensures the payload remains attached to the antibody. The compound itself does not exhibit direct cellular activity but enables the bioactivity of the conjugated therapeutic agent. |
| ln Vivo |
In vivo activity of Mal-Ph-CONH-PEG4-NHS ester is realized through the ADC constructs in which it is incorporated. As a non-cleavable linker, it provides stability to the ADC in circulation, ensuring the cytotoxic payload remains attached until target cell engagement. The PEG4 spacer improves the pharmacokinetic properties of the conjugate. The in vivo efficacy depends on the specific antibody and payload used in the conjugate.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Mal-Ph-CONH-PEG4-NHS ester focus on evaluating the stability and reactivity of the linker. The compound is tested for its ability to conjugate to thiol- and amine-containing molecules. The conjugation efficiency is monitored by HPLC or mass spectrometry. The stability of the linker under physiological conditions is also assessed by incubating in buffer solutions at 37°C.
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| Cell Assay |
In vitro cellular assays for Mal-Ph-CONH-PEG4-NHS ester involve testing the complete ADC molecule rather than the linker alone. Cancer cell lines are treated with the ADC, and cell viability is assessed using CCK-8 or MTT assays after 72 hours. The linker's contribution to ADC activity is evaluated by comparing the activity of the ADC with that of the unconjugated payload. The linker itself does not directly affect cell viability but is essential for the function of the conjugated therapeutic molecule.
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| Animal Protocol |
In vivo animal studies for Mal-Ph-CONH-PEG4-NHS ester are conducted using the final ADC construct. Tumor-bearing xenograft models receive the ADC via intravenous injection. Tumor volume and body weight are monitored over 2-4 weeks to assess efficacy and tolerability. The linker contributes to the stability and PK profile of the ADC. Detailed in vivo protocols are similar to those used for other ADC linkers.
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| ADME/Pharmacokinetics |
Mal-Ph-CONH-PEG4-NHS ester has a molecular formula of C27H32N4O12 and a molecular weight of 561.54. It has a purity of ≥97%. It appears as a solid at room temperature. The compound is soluble in DMSO and other organic solvents. It is stable under recommended storage conditions. It is intended for research use only and is not approved for clinical use.
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| Toxicity/Toxicokinetics |
The toxicity profile of Mal-Ph-CONH-PEG4-NHS ester is associated with the ADC in which it is used. As a linker compound, it is considered to have low intrinsic toxicity. Standard toxicity studies for the final ADC include assessment of body weight changes, clinical observations, hematological parameters, and histopathological examination of major organs in animal models. The linker itself does not exhibit significant cytotoxic effects in standard cell viability assays.
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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 May;16(5):315-337.
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| Additional Infomation |
Mal-Ph-CONH-PEG4-NHS ester (CAS 1263044-88-7) is a non-cleavable 4-unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). It features a maleimide group that selectively reacts with thiols, an NHS ester that couples with primary amines, and a PEG4 spacer. It is widely used in bioconjugation and chemical biology. It is intended for research use only and is not approved for clinical use.
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| Molecular Formula |
C26H31N3O11
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|---|---|
| Exact Mass |
561.195
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| CAS # |
1263044-88-7
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| PubChem CID |
51341014
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| Appearance |
Colorless to light yellow liquid
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| LogP |
-1.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
40
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| Complexity |
920
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)N(C1=O)OC(=O)CCOCCOCCOCCOCCNC(=O)C2=CC(=CC=C2)N3C(=O)C=CC3=O
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| InChi Key |
QDLKNPCHCJFKOJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H31N3O11/c30-21-4-5-22(31)28(21)20-3-1-2-19(18-20)26(35)27-9-11-37-13-15-39-17-16-38-14-12-36-10-8-25(34)40-29-23(32)6-7-24(29)33/h1-5,18H,6-17H2,(H,27,35)
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| Chemical Name |
(2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[[3-(2,5-dioxopyrrol-1-yl)benzoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
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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.) |
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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