| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Protease Cleavable Linker
Cleavable Linker Fmoc-Val-Cit-PAB-PNP targets the enzyme cathepsin B, which is overexpressed in lysosomes of cancer cells. As a cleavable ADC linker, its "target" is the proteolytic activity of cathepsin B. The enzyme recognizes and cleaves the Val-Cit dipeptide sequence, triggering a self-immolative reaction that releases the PAB spacer and the attached payload. This mechanism ensures targeted drug delivery. |
|---|---|
| ln Vitro |
A lysosome enzyme can break down the peptide sequence found in Fmoc-Val-Cit-PAB-PNP[1].
The peptide bond between Cit-PAB of dipeptide linkers containing Valine (Val)-citrulline (Cit) and p-aminobenzyl alcohol (PAB) is broken by cathepsin B in the lysosome. When a medication and PAB are covalently bound together by carbamate bonds, the drug can be liberated through hydrolysis following Cit-PAB peptide bond cleavage. Using this mechanism, antibody-drug conjugates (ADCs) have been developed[2]. As a chemical linker, Fmoc-Val-Cit-PAB-PNP does not have intrinsic biological activity. Its in vitro activity is assessed by its cleavage efficiency by cathepsin B in enzymatic assays. The linker is characterized by superior plasma stability, comparable to that of non-cleavable linkers. It is rapidly and selectively cleaved in the presence of cathepsin B. |
| ln Vivo |
Prior to designing successful efficacy and safety studies in rodents during preclinical stages of ADC programs, mice must stabilize the Fmoc-Val-Cit-PAB-PNP linker[3].
The VC-PABC linker's stability in mouse plasma is largely determined by its conjugation site, and both in vitro and in vivo, the linker's stability and ADC's cytotoxic potency are positively correlated[3]. In vivo, Fmoc-Val-Cit-PAB-PNP is evaluated as part of an ADC. The linker's stability in circulation and its ability to release the payload specifically in the tumor microenvironment are critical for the ADC's efficacy and safety. The Val-Cit linker enables targeted drug delivery to cancer cells, improving the therapeutic index. The PNP group is used to activate the linker for conjugation to the payload. |
| Enzyme Assay |
In vitro enzyme assays for Fmoc-Val-Cit-PAB-PNP involve incubating the linker-payload conjugate with purified cathepsin B. The cleavage of the Val-Cit dipeptide is monitored by HPLC or LC-MS. These assays confirm the linker's susceptibility to the target enzyme and quantify the rate of payload release.
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| Cell Assay |
In vitro cell-based assays for Fmoc-Val-Cit-PAB-PNP are performed on ADCs containing this linker. The ADC is added to cancer cell cultures. The release of the cytotoxic payload is measured by assessing cell viability or by detecting the free drug. These assays confirm intracellular cleavage and target cell death.
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| Animal Protocol |
In vivo animal experiments for Fmoc-Val-Cit-PAB-PNP are conducted using ADCs that incorporate this linker. Tumor-bearing mice are treated with the ADC, and tumor growth inhibition is monitored. The linker's stability in circulation and its ability to deliver the payload are assessed through pharmacokinetic and biodistribution studies.
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| ADME/Pharmacokinetics |
Fmoc-Val-Cit-PAB-PNP has a molecular weight of 766.80 and a molecular formula of C40H42N6O10. It has an appearance of a white to light yellow powder to crystal and is typically stored at -20°C. Its purity is ≥95.0% by HPLC. It is soluble in DMSO and water.
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| Toxicity/Toxicokinetics |
Fmoc-Val-Cit-PAB-PNP is not a drug and has no associated toxicity data. It is a research-grade chemical for laboratory use. Standard safety precautions should be taken when handling. It is not intended for human or veterinary use.
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| References |
[4]. Sano K, Nakajima T, Miyazaki K, Ohuchi Y, Ikegami T, Choyke PL, Kobayashi H. Short PEG-linkers improve the performance of targeted, activatable monoclonal antibody-indocyanine green optical imaging probes. Bioconjug Chem. 2013 May 15;24(5):811-6. doi: 10.1021/bc400050k. Epub 2013 May 3. PubMed PMID: 23600922; PubMed Central PMCID: PMC3674550.
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| Additional Infomation |
Fmoc-Val-Cit-PAB-PNP is a cathepsin B-sensitive ADC linker. It is a highly stable, cleavable linker used in advanced ADC development. The Val-Cit dipeptide is cleaved by cathepsin B in tumor cells, enabling selective payload release. The PNP group acts as a leaving group for conjugation to the drug payload. This linker is suitable for developing ADCs requiring precision and tumor-selective release.
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| Molecular Formula |
C40H42N6O10
|
|---|---|
| Molecular Weight |
766.795690059662
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| Exact Mass |
766.3
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| Elemental Analysis |
C, 62.65; H, 5.52; N, 10.96; O, 20.86
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| CAS # |
863971-53-3
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| Related CAS # |
863971-53-3;
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| PubChem CID |
57641184
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| Appearance |
White to yellow solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
56
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| Complexity |
1320
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)[C@@H](C(=O)N[C@@H](CCCNC(=O)N)C(=O)NC1=CC=C(C=C1)COC(=O)OC2=CC=C(C=C2)[N+](=O)[O-])NC(=O)OCC3C4=CC=CC=C4C5=CC=CC=C35
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| InChi Key |
USMYACISHVPTHK-SFCXHYMASA-N
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| InChi Code |
InChI=1S/C40H42N6O10/c1-24(2)35(45-39(50)54-23-33-31-10-5-3-8-29(31)30-9-4-6-11-32(30)33)37(48)44-34(12-7-21-42-38(41)49)36(47)43-26-15-13-25(14-16-26)22-55-40(51)56-28-19-17-27(18-20-28)46(52)53/h3-6,8-11,13-20,24,33-35H,7,12,21-23H2,1-2H3,(H,43,47)(H,44,48)(H,45,50)(H3,41,42,49)/t34-,35?/m0/s1
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| Chemical Name |
(9H-fluoren-9-yl)methyl ((S)-3-methyl-1-(((S)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-1-oxobutan-2-yl)carbamate
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| HS Tariff Code |
2934.99.03.00
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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 (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 : ≥ 40 mg/mL (~52.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.25 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 52.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 10% DMSO+ 90% corn oil: ≥ 5.25 mg/mL (6.85 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3041 mL | 6.5206 mL | 13.0412 mL | |
| 5 mM | 0.2608 mL | 1.3041 mL | 2.6082 mL | |
| 10 mM | 0.1304 mL | 0.6521 mL | 1.3041 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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