| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Fmoc-Val-Ala-PAB targets the enzyme cathepsin B, which is overexpressed in lysosomes of tumor cells. As a cleavable ADC linker, its "target" is the proteolytic activity of cathepsin B, which recognizes and cleaves the Val-Ala dipeptide sequence. This enzyme-mediated cleavage triggers the release of the PAB spacer and the subsequent release of the cytotoxic payload, ensuring targeted drug delivery.
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|---|---|
| ln Vitro |
ADC cytotoxins are connected to antibodies through an ADC connector to form ADCs [1].
As a chemical linker, Fmoc-Val-Ala-PAB does not have its own biological activity. Its "in vitro activity" is demonstrated by its efficient cleavage by cathepsin B in biochemical assays. The linker is stable in plasma but is rapidly cleaved in the presence of the enzyme, releasing the payload. This selective cleavage profile is a key feature for its use in ADC development. |
| ln Vivo |
In vivo, Fmoc-Val-Ala-PAB 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. When conjugated to an antibody and a cytotoxic drug, the Val-Ala-PAB linker enables targeted drug delivery to cancer cells, improving therapeutic index.
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| Enzyme Assay |
In vitro enzyme assays for Fmoc-Val-Ala-PAB involve incubating the linker or a linker-payload conjugate with purified cathepsin B. The cleavage of the Val-Ala dipeptide is monitored by HPLC or LC-MS to quantify the rate and efficiency of payload release. This assay confirms the linker's susceptibility to the target enzyme.
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| Cell Assay |
In vitro cell-based assays for Fmoc-Val-Ala-PAB are performed on ADCs containing this linker. The ADC is added to cancer cell cultures, and the release of the cytotoxic payload is measured by assessing cell viability (e.g., MTT assay) or by detecting the free drug in the media. These assays confirm that the linker is cleaved intracellularly, leading to target cell death.
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| Animal Protocol |
In vivo animal experiments for Fmoc-Val-Ala-PAB are conducted using ADCs that incorporate this linker. Tumor-bearing mice are treated with the ADC, and efficacy (tumor growth inhibition) and toxicity are monitored. The linker's stability in circulation and its ability to deliver the payload to the tumor are assessed through pharmacokinetic and biodistribution studies.
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| ADME/Pharmacokinetics |
Fmoc-Val-Ala-PAB has a molecular weight of 515.61 and a molecular formula of C30H33N3O5. It has a melting point of 218°C (dec.) and is typically stored at -20°C under nitrogen. It is light, moisture, and heat sensitive. The compound is soluble in DMSO.
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| Toxicity/Toxicokinetics |
Fmoc-Val-Ala-PAB 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 | |
| Additional Infomation |
Fmoc-Val-Ala-PAB is a cleavable ADC linker containing a Val-Ala dipeptide sequence. The Val-Ala sequence is a substrate for cathepsin B, an enzyme overexpressed in tumor cells, enabling the selective release of the cytotoxic payload. The PAB spacer ensures efficient release of the drug after enzymatic cleavage. This linker is compatible with standard peptide synthesis methods and is a versatile tool for ADC development.
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| Molecular Formula |
C30H33N3O5
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|---|---|
| Molecular Weight |
515.61
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| Exact Mass |
515.242
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| Elemental Analysis |
C, 69.88; H, 6.45; N, 8.15; O, 15.51
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| CAS # |
1394238-91-5
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| PubChem CID |
100029287
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| Appearance |
White to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
811.1±65.0 °C at 760 mmHg
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| Melting Point |
218 °C(dec.)
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| Flash Point |
444.4±34.3 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.620
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| LogP |
4.13
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
38
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| Complexity |
790
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C(N[C@H](C(N[C@H](C(NC1C=CC(CO)=CC=1)=O)C)=O)C(C)C)=O)CC1C2C=CC=CC=2C2=CC=CC=C12
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| InChi Key |
PIEQFKSWCKVBTP-PPHZAIPVSA-N
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| InChi Code |
InChI=1S/C30H33N3O5/c1-18(2)27(29(36)31-19(3)28(35)32-21-14-12-20(16-34)13-15-21)33-30(37)38-17-26-24-10-6-4-8-22(24)23-9-5-7-11-25(23)26/h4-15,18-19,26-27,34H,16-17H2,1-3H3,(H,31,36)(H,32,35)(H,33,37)/t19-,27-/m0/s1
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| Chemical Name |
9H-fluoren-9-ylmethyl N-[(2S)-1-[[(2S)-1-[4-(hydroxymethyl)anilino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
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| Synonyms |
Fmoc-Val-Ala-PAB-OH; ACD linker; Fmoc-Val-Ala-PAB
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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 : ~33.33 mg/mL (~64.64 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.56 mg/mL (1.09 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 5.6 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: ≥ 0.56 mg/mL (1.09 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 5.6 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 | 1.9395 mL | 9.6973 mL | 19.3945 mL | |
| 5 mM | 0.3879 mL | 1.9395 mL | 3.8789 mL | |
| 10 mM | 0.1939 mL | 0.9697 mL | 1.9395 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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