| Size | Price | Stock | Qty |
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| Targets |
Protease Cleavable Linker
Cleavable Linker Mc-Val-Ala-PAB does not have a direct biological target itself; it is a chemical tool. Its role is to enable targeted drug delivery. The Val-Ala dipeptide within the linker is the key functional group that acts as a substrate for specific proteases, such as cathepsin B, which are often overexpressed in the tumor microenvironment. Upon internalization of the ADC into the target cell, the linker is cleaved by these enzymes, releasing the cytotoxic payload to exert its therapeutic effect. |
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| ln Vitro |
ADCs are made up of an antibody and an ADC cytotoxin that are joined together by an ADC linker[1].
In vitro, Mc-Val-Ala-PAB is used as a chemical reagent to construct ADCs. Its activity is not measured directly, but rather through the efficacy of the complete ADC. The linker's performance is characterized by its ability to be conjugated to antibodies and its stability in circulation. It is also evaluated for its specific cleavage by target enzymes, which is crucial for the controlled release of the drug. Its function as a cleavable linker is a key feature in ADC development. |
| ln Vivo |
In vivo, Mc-Val-Ala-PAB is not administered as a therapeutic agent on its own. Its in vivo behavior is determined by the complete ADC molecule of which it is a part. The linker's role is to remain stable in the bloodstream to prevent premature release of the payload, but to be efficiently cleaved once the ADC is internalized by the target cancer cell. This targeted delivery is central to the therapeutic strategy of ADCs, aiming to increase efficacy and reduce systemic toxicity.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies are not applicable to Mc-Val-Ala-PAB itself. However, its function is often validated in biochemical assays that test the cleavage of the Val-Ala dipeptide by specific proteases like cathepsin B. In these assays, the linker or the complete ADC is incubated with the enzyme, and the release of the payload or a surrogate marker is measured. This confirms the linker's susceptibility to enzymatic cleavage, which is a critical feature for its function in ADCs.
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| Cell Assay |
In vitro cellular assays for Mc-Val-Ala-PAB are not performed on the linker alone. The activity of the linker is assessed as part of a complete ADC. In these assays, cancer cells expressing the target antigen are treated with the ADC. The key readouts are cytotoxicity (cell viability assays like MTT or CellTiter-Glo) and the specificity of the effect, which is confirmed by comparing to a non-targeting control ADC. The success of the linker is demonstrated by the potent and selective killing of the target cells.
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| Animal Protocol |
In vivo animal studies for Mc-Val-Ala-PAB are not conducted on the linker alone. Its performance is evaluated through the in vivo efficacy of the complete ADC in xenograft mouse models. Tumor-bearing mice are treated with the ADC, and endpoints include tumor volume reduction, survival, and pharmacokinetic analysis. These studies are critical for demonstrating that the linker enables the ADC to deliver the payload effectively to the tumor while maintaining stability in circulation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mc-Val-Ala-PAB are not characterized independently, as it is a linker. Its properties influence the PK of the complete ADC. Key characteristics include its molecular weight (486.56 g/mol) and formula (C₂₅H₃₄N₄O₆). The linker's stability in plasma is crucial for the ADC's circulation half-life, and its cleavage rate by intracellular proteases determines the rate of drug release. These properties are optimized to ensure the ADC has a favorable therapeutic index.
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| Toxicity/Toxicokinetics |
Toxicological data for Mc-Val-Ala-PAB are not available for the linker itself, as it is a chemical building block. Its safety profile is assessed as part of the complete ADC. The primary toxicity concerns are related to the cytotoxic payload and its potential for premature release. The use of a cleavable linker like Mc-Val-Ala-PAB is intended to minimize systemic toxicity by ensuring the payload is released primarily within the target cells.
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| References | |
| Additional Infomation |
Mc-Val-Ala-PAB is a research-use-only chemical compound that serves as a crucial component in the development of ADCs. Its design as a cleavable linker with a Val-Ala dipeptide and a PAB spacer is a common strategy in ADC technology. The maleimide group allows for site-specific conjugation to antibodies. This linker is used in the synthesis of active antibody-conjugated molecules for targeted drug delivery. It is not approved for human use and is strictly a research tool.
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| Molecular Formula |
C25H34N4O6
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|---|---|
| Molecular Weight |
486.560666561127
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| Exact Mass |
486.247
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| Elemental Analysis |
C, 61.71; H, 7.04; N, 11.51; O, 19.73
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| CAS # |
1870916-87-2
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| Related CAS # |
1870916-87-2
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| PubChem CID |
100029273
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| Appearance |
Off-white to yellow solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
35
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| Complexity |
786
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H](C(=O)NC1=CC=C(C=C1)CO)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN2C(=O)C=CC2=O
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| InChi Key |
DAMSURYLURICHN-SBUREZEXSA-N
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| InChi Code |
InChI=1S/C25H34N4O6/c1-16(2)23(28-20(31)7-5-4-6-14-29-21(32)12-13-22(29)33)25(35)26-17(3)24(34)27-19-10-8-18(15-30)9-11-19/h8-13,16-17,23,30H,4-7,14-15H2,1-3H3,(H,26,35)(H,27,34)(H,28,31)/t17-,23-/m0/s1
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| Chemical Name |
6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)hexanamide
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| Synonyms |
Mc-Val-Ala-PAB, Mc-Val-Ala-PAB-OH; ACD linker.
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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 | 2.0552 mL | 10.2762 mL | 20.5524 mL | |
| 5 mM | 0.4110 mL | 2.0552 mL | 4.1105 mL | |
| 10 mM | 0.2055 mL | 1.0276 mL | 2.0552 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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