| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
MC-Val-Ala-PAB-PNP does not possess a specific pharmacological target of its own. Its function is structural and chemical—it serves as a cleavable linker that connects an antibody to a cytotoxic payload in an ADC. The Val-Ala dipeptide sequence is recognized and cleaved by cathepsin B, a lysosomal protease that is overexpressed in many tumor cells. Upon internalization of the ADC into the target cell and trafficking to the lysosome, cathepsin B cleaves the peptide linker, releasing the cytotoxic payload specifically within the tumor cell. The PAB spacer provides a self-immolative release mechanism: upon cleavage of the peptide bond, the PAB group spontaneously eliminates to release the free payload. The maleimide group enables site-specific conjugation to thiol groups on antibodies.
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| ln Vitro |
The ADC is made up of a preamp to which the ADC input connects the ADC cytotoxin [1].
The in vitro activity of MC-Val-Ala-PAB-PNP is evaluated in the context of ADC synthesis and function rather than as a direct biological agent. The compound is used to synthesize ADC linkers, and the resulting ADCs are tested for their ability to bind to target antigens on cancer cells, undergo internalization, and deliver cytotoxic payloads. The cathepsin B-cleavable nature of the Val-Ala sequence can be confirmed in vitro by incubating the ADC or a model substrate with recombinant cathepsin B and analyzing the cleavage products by HPLC or mass spectrometry. The selectivity of cleavage (over other proteases) is also assessed. The PAB self-immolative mechanism can be confirmed by analyzing the release of the payload upon cleavage. The linker's stability in plasma is evaluated to ensure that the linker is not prematurely cleaved in circulation. |
| ln Vivo |
In vivo activity of MC-Val-Ala-PAB-PNP is realized through the ADCs constructed using this linker. ADC molecules containing this peptide linker are evaluated in mouse xenograft models bearing tumors that express the target antigen. The ADCs are administered via intravenous injection at various doses, and antitumor efficacy is assessed by measuring tumor volume changes over time. The cathepsin B-cleavable nature of the Val-Ala linker is expected to result in selective payload release within tumor cells, minimizing systemic toxicity. Pharmacodynamic endpoints include measurement of tumor growth inhibition, assessment of apoptosis markers in tumor tissues, and evaluation of payload distribution in tumors versus normal tissues. The Val-Ala linker has been validated in multiple ADC programs, including FDA-approved ADCs.
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| Enzyme Assay |
Characterization of MC-Val-Ala-PAB-PNP involves standard analytical techniques for peptide-based linkers. Purity is typically assessed by HPLC, with the compound available at ≥98% purity. Nuclear magnetic resonance (NMR) spectroscopy (¹H and ¹³C) confirms the chemical structure, while mass spectrometry (MS) provides accurate molecular weight confirmation. The maleimide group can be detected by UV absorbance (characteristic at ~300 nm), while the PNP group can be detected by UV absorbance. The compound's molecular weight is 651.66 and its molecular formula is C32H37N5O10. The compound should be stored under appropriate conditions to maintain stability and prevent maleimide hydrolysis and PNP carbonate hydrolysis.
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| Cell Assay |
Cell-based studies involving MC-Val-Ala-PAB-PNP are typically conducted in the context of ADC development. The compound is used to synthesize ADC linkers, and the resulting ADCs are evaluated in cell lines expressing the target antigen. Cell-based assays include binding affinity measurements (by flow cytometry or surface plasmon resonance), internalization studies (by confocal microscopy or flow cytometry), and cytotoxicity assays (by MTT or CellTiter-Glo). The specificity of the ADC for antigen-positive versus antigen-negative cells is assessed to confirm target-dependent activity. The cathepsin B-cleavable nature of the Val-Ala linker can be verified by comparing the activity of the ADC in cells treated with cathepsin B inhibitors versus untreated cells. The PAB self-immolative mechanism contributes to efficient payload release.
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| Animal Protocol |
In vivo studies with ADCs incorporating MC-Val-Ala-PAB-PNP are typically performed in mouse xenograft models. Immunodeficient mice are implanted with human tumor cell lines expressing the target antigen, and after tumors reach a certain size, ADCs are administered intravenously at various doses and schedules. Antitumor efficacy is assessed by measuring tumor volumes, and toxicity is evaluated by monitoring body weight, clinical signs, and histopathological examination of organs. Pharmacokinetic studies are conducted to measure ADC and payload concentrations in plasma and tissues. The Val-Ala linker's in vivo stability and payload release kinetics are evaluated by measuring free payload levels in tumors versus normal tissues. The linker's performance is compared to other cleavable and non-cleavable linkers to optimize ADC design.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MC-Val-Ala-PAB-PNP itself are not typically characterized, as the compound is a building block rather than a drug candidate. In the context of ADCs, the peptide linker contributes to the overall stability and pharmacokinetics of the ADC conjugate. The Val-Ala sequence is designed to be stable in circulation (where cathepsin B activity is low) and cleavable in the lysosomal compartment (where cathepsin B activity is high). The PAB self-immolative spacer ensures efficient payload release upon cleavage. Storage recommendations include appropriate temperature control to maintain stability and prevent hydrolysis of the maleimide and PNP carbonate groups. The compound should be handled under anhydrous conditions to prevent hydrolysis.
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| Toxicity/Toxicokinetics |
As a research chemical, MC-Val-Ala-PAB-PNP is not intended for human or veterinary use, and comprehensive toxicological data are not extensively reported in the available literature. Standard laboratory safety precautions should be followed when handling the compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety glasses) and proper ventilation. The compound contains a maleimide group, which can be a skin sensitizer, and a PNP carbonate, which should be handled with care. The compound is not classified as hazardous under normal handling conditions, but should be handled with care. It should be stored under recommended conditions to maintain stability and prevent hydrolysis.
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| References | |
| Additional Infomation |
MC-Val-Ala-PAB-PNP is a cleavable peptide-based ADC linker featuring a maleimide group for antibody conjugation, a Val-Ala dipeptide for cathepsin B cleavage, a PAB spacer for self-immolative release, and a PNP carbonate for payload conjugation. It is classified as a cleavable ADC linker and is used in the synthesis of antibody-drug conjugates. The compound is widely applied in ADC development for targeted cancer therapy. It is not approved for clinical use as a standalone compound but is used in the synthesis of ADC therapeutics. The compound is available from multiple chemical suppliers.
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| Molecular Formula |
C32H37N5O10
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| Molecular Weight |
651.663688421249
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| Exact Mass |
651.254
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| CAS # |
1639939-40-4
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| PubChem CID |
100029269
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
47
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| Complexity |
1150
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C([C@H](C(C)C)NC(CCCCCN1C(C=CC1=O)=O)=O)N(C1C=CC(COC(=O)OC2C=CC(=CC=2)[N+](=O)[O-])=CC=1)[C@H](C(N)=O)C
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| InChi Key |
QXMLUPPUFBNKRY-LGGPFLRQSA-N
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| InChi Code |
InChI=1S/C32H37N5O10/c1-20(2)29(35-26(38)7-5-4-6-18-36-27(39)16-17-28(36)40)31(42)33-21(3)30(41)34-23-10-8-22(9-11-23)19-46-32(43)47-25-14-12-24(13-15-25)37(44)45/h8-17,20-21,29H,4-7,18-19H2,1-3H3,(H,33,42)(H,34,41)(H,35,38)/t21-,29-/m0/s1
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| Chemical Name |
[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate
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| Synonyms |
MCValAlaPABPNP; MC Val Ala PAB PNP
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~76.73 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (3.19 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5345 mL | 7.6727 mL | 15.3454 mL | |
| 5 mM | 0.3069 mL | 1.5345 mL | 3.0691 mL | |
| 10 mM | 0.1535 mL | 0.7673 mL | 1.5345 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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