| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Protease Cleavable Linker
Cleavable Linker Boc-Val-Cit-PAB-PNP is a linker molecule used in antibody-drug conjugates (ADCs) for the targeted delivery of cytotoxic drugs. The Val-Cit dipeptide is a substrate for cathepsin B, which is overexpressed in many tumors. The linker is cleaved by cathepsin B in the lysosomes of target cells, releasing the drug. The PNP carbonate reacts with amines to form carbamates or carbonates. |
|---|---|
| ln Vitro |
ADCs are made up of an antibody and an ADC cytotoxin that are joined together by an ADC linker[1].
In vitro activity of Boc-Val-Cit-PAB-PNP is not applicable as the compound is a chemical linker rather than a biologically active drug. However, ADCs containing this linker have demonstrated potent anti-tumor activity in vitro. The linker is stable in circulation and is efficiently cleaved by cathepsin B in the lysosomes of cancer cells, releasing the cytotoxic payload. |
| ln Vivo |
In vivo, ADCs containing the Val-Cit-PAB linker have shown potent anti-tumor activity in animal models of cancer. The linker is stable in circulation, minimizing off-target toxicity, and is efficiently cleaved in the tumor microenvironment, releasing the drug specifically in cancer cells.
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| Enzyme Assay |
In vitro enzyme assays for Boc-Val-Cit-PAB-PNP involve measuring the cleavage of the Val-Cit dipeptide by cathepsin B. The linker is incubated with recombinant cathepsin B, and the cleavage products are analyzed by HPLC or mass spectrometry. The rate of cleavage is determined to assess the linker's susceptibility to enzymatic degradation.
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| Cell Assay |
Cell-based assays for Boc-Val-Cit-PAB-PNP involve the evaluation of ADCs containing the linker in cancer cell lines. Cells are treated with the ADC, and cell viability, proliferation, and apoptosis are assessed. The selectivity of the ADC for cancer cells over normal cells is also evaluated.
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| Animal Protocol |
In vivo animal studies for Boc-Val-Cit-PAB-PNP involve the evaluation of ADCs containing the linker in tumor xenograft models. Immunocompromised mice are implanted with human cancer cells and treated with the ADC. Tumor growth, survival, and toxicity are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Boc-Val-Cit-PAB-PNP itself are not applicable as it is a chemical linker. However, ADCs containing this linker have favorable pharmacokinetic properties, including stability in circulation and efficient release of the drug in the tumor. The linker is designed to be cleaved specifically by cathepsin B, minimizing systemic toxicity.
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| Toxicity/Toxicokinetics |
Toxicological data for Boc-Val-Cit-PAB-PNP are derived from studies of ADCs containing the linker. The linker is designed to be stable in circulation and to release the drug specifically in the tumor, minimizing off-target toxicity. However, ADCs may have potential toxicities related to the payload or the antibody.
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| References | |
| Additional Infomation |
Boc-Val-Cit-PAB-PNP (CAS# 870487-10-8) is a cleavable linker containing a Val-Cit dipeptide, a PAB spacer, and a PNP carbonate. It is used in the synthesis of ADCs for targeted drug delivery. The Val-Cit dipeptide is cleaved by cathepsin B in the tumor microenvironment, releasing the drug specifically in cancer cells. The compound is for research use only.
|
| Molecular Formula |
C30H40N6O10
|
|---|---|
| Molecular Weight |
644.682
|
| Exact Mass |
644.28
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| Elemental Analysis |
C, 55.89; H, 6.25; N, 13.04; O, 24.82
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| CAS # |
870487-10-8
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| PubChem CID |
75412383
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| Appearance |
White to off-white to be determined
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| LogP |
3.5
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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 |
17
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| Heavy Atom Count |
46
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
2
|
| 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)OC(C)(C)C
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| InChi Key |
SKWLDDHVHXQPOG-ZEQRLZLVSA-N
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| InChi Code |
InChI=1S/C30H40N6O10/c1-18(2)24(35-28(40)46-30(3,4)5)26(38)34-23(7-6-16-32-27(31)39)25(37)33-20-10-8-19(9-11-20)17-44-29(41)45-22-14-12-21(13-15-22)36(42)43/h8-15,18,23-24H,6-7,16-17H2,1-5H3,(H,33,37)(H,34,38)(H,35,40)(H3,31,32,39)/t23-,24-/m0/s1
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| Chemical Name |
tert-Butyl ((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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| Synonyms |
BocValCitPABPNP Boc Val Cit 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: 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 : ~100 mg/mL (~155.12 mM ）
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.23 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 10% DMSO+ 90% (20% SBE-β-CD in saline): ≥ 2.08 mg/mL (3.23 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5512 mL | 7.7558 mL | 15.5116 mL | |
| 5 mM | 0.3102 mL | 1.5512 mL | 3.1023 mL | |
| 10 mM | 0.1551 mL | 0.7756 mL | 1.5512 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.
Products are for research use only; We do not sell to patients
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