| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Mal-PEG8-Val-Ala-PABC does not target a biological receptor; it is a chemical linker used to conjugate cytotoxic payloads to antibodies. The Val-Ala dipeptide is specifically recognized and cleaved by cathepsin proteases in lysosomes, enabling intracellular drug release. This linker is used in the synthesis of Tesirine.
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| ln Vitro |
Not available. As a linker, its activity is evaluated in the context of an ADC conjugate. Upon antibody-mediated internalization and trafficking to lysosomes, cathepsin proteases cleave the Val-Ala dipeptide, initiating the PABC self-immolative elimination that releases the attached payload. This mechanism ensures minimal premature drug release in circulation.
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| ln Vivo |
Not available. ADCs constructed using Mal-PEG8-Val-Ala-PABC (such as Tesirine-based ADCs) have demonstrated in vivo anti-tumor efficacy in preclinical xenograft models. The PEG8 spacer improves pharmacokinetic properties and therapeutic window compared to shorter PEG linkers by reducing aggregation and optimizing drug-to-antibody ratio.
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| Enzyme Assay |
Not available. Standard cathepsin cleavage assays involve incubating Mal-PEG8-Val-Ala-PABC-payload conjugates (1-50 uM) with recombinant cathepsin B or L (10-100 nM) in 50 mM sodium acetate buffer (pH 5.0-5.5) containing 2 mM DTT at 37degC for 2-24 hours, followed by HPLC-MS analysis of released payload. Maleimide conjugation efficiency is confirmed by MALDI-TOF mass spectrometry.
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| Cell Assay |
Not available. For ADC activity assessment, typical protocols involve treating antigen-positive cancer cells with ADCs containing Mal-PEG8-Val-Ala-PABC (0.001-100 nM) for 72-120 hours, then measuring cell viability. Cathepsin dependence is confirmed using cathepsin inhibitors (e.g., E-64d) or cathepsin B-knockout cell lines.
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| Animal Protocol |
Not available. For in vivo studies, standard protocols involve intravenous administration of Mal-PEG8-Val-Ala-PABC-based ADCs (1-30 mg/kg) in tumor-bearing mice, with efficacy assessed by tumor volume measurement twice weekly. Pharmacokinetic studies assess stability in circulation by measuring antibody-conjugated payload levels in plasma at various time points (e.g., 1, 24, 48, 96, 168 hours).
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| ADME/Pharmacokinetics |
Not available. The PEG8 linker improves solubility and reduces aggregation, which can improve ADC circulation half-life compared to non-PEGylated linkers. The Val-Ala-PABC linker exhibits high stability in serum (typically >95% intact at 37degC for 7-14 days) with rapid cleavage upon lysosomal internalization (within 1-4 hours).
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| Toxicity/Toxicokinetics |
Toxicity of ADCs containing Mal-PEG8-Val-Ala-PABC is primarily determined by the payload and antibody specificity. The linker itself has minimal intrinsic toxicity. PEG8 reduces immunogenicity risk compared to shorter PEG chains. Specific toxicological data for this linker alone are not available.
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| References |
[1]. Congreve, S., et al. Antibody drug conjugates (ADC): Current status and mapping of ADC:s in clinical programs.
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| Additional Infomation |
Mal-PEG8-Val-Ala-PABC is a research-grade cleavable ADC linker used in the synthesis of Tesirine, a drug-linker conjugate for ADC development. It has not been individually approved for clinical use but is a component in ADC research platforms. The PEG8 spacer is selected for optimal solubility and conjugation properties. This product is for laboratory research only.
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| Molecular Formula |
C41H65N5O15
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|---|---|
| Appearance |
Colorless to light pink viscous liquid
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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, 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 :~100 mg/mL (~115.21 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.) |
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
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