| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
| Targets |
Disulfide Cleavable Linker
PDP-Pfp targets the extracellular loop 1 (ECL1) of TM4SF1, a member of the transmembrane 4 L6 family. TM4SF1 is a cell surface protein that is overexpressed in various cancers and is involved in tumor progression and metastasis. As an ADC linker, PDP-Pfp enables the conjugation of cytotoxic payloads to targeting agents that recognize TM4SF1, facilitating selective delivery of drugs to cancer cells. The reducible disulfide bond provides a mechanism for intracellular drug release upon exposure to the reducing environment of the cytosol. |
|---|---|
| ln Vitro |
In vitro activity of PDP-Pfp is assessed by its ability to form stable conjugates with targeting agents and its selective cleavage in reducing environments. The efficiency of conjugation to antibodies or targeting proteins is evaluated by SDS-PAGE, mass spectrometry, and HPLC. The reducible nature of the disulfide bond is confirmed by incubation with reducing agents such as DTT or glutathione, followed by analysis of conjugate stability. Cell binding and internalization studies are conducted using target-positive and target-negative cell lines to assess specificity.
|
| ln Vivo |
In vivo studies for PDP-Pfp are typically conducted as part of complete ADC development targeting TM4SF1-positive tumors. The ADC is evaluated in mouse xenograft models bearing TM4SF1-expressing human tumors. Efficacy is assessed by tumor growth inhibition, and pharmacokinetic studies evaluate the stability of the linker in circulation. The reducible nature of the disulfide bond is designed to maintain stability in the oxidative extracellular environment while enabling drug release in the reducing intracellular environment of target cells.
|
| Enzyme Assay |
For conjugation assays, PDP-Pfp is dissolved in anhydrous DMSO or DMF and added to a solution of antibody or targeting protein in PBS buffer. The reaction is incubated at room temperature for 2-4 hours, and the extent of conjugation is monitored by SDS-PAGE or MALDI-TOF mass spectrometry. For disulfide cleavage studies, the conjugate is incubated with various concentrations of glutathione or DTT, and the release of payload is analyzed by HPLC or LC-MS. The stability of the conjugate in plasma is assessed by incubation in mouse or human plasma at 37°C.
|
| Cell Assay |
Target-positive cancer cell lines expressing TM4SF1 are cultured in appropriate media. Cells are treated with PDP-Pfp-containing ADC conjugates at various concentrations for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays, and IC50 values are calculated. Cell binding is evaluated by flow cytometry using fluorescently labeled conjugates, and internalization is assessed using confocal microscopy or pH-sensitive dyes. Apoptosis induction is measured by caspase-3/7 activity or Annexin V staining.
|
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice bearing TM4SF1-positive tumor xenografts are administered the complete ADC (containing PDP-Pfp as the linker) via intravenous injection. Dosing typically involves multiple injections at 1-2 week intervals. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study termination, tumors and major organs are collected for histopathological analysis and drug concentration measurement. Pharmacokinetic studies assess ADC stability and drug release in circulation.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of PDP-Pfp are characterized as part of the complete ADC. The compound has a predicted density of 1.54 g/cm3. The reducible disulfide bond provides a mechanism for intracellular drug release while maintaining stability in circulation. The perfluorophenyl ester group enhances reactivity with amines on targeting agents. The linker's performance in terms of circulation half-life, stability, and drug release kinetics depends on the specific antibody and payload used. Storage at 2-8°C is recommended.
|
| Toxicity/Toxicokinetics |
PDP-Pfp is a chemical reagent intended for research use only and is not approved for human therapeutic use. As a reducible ADC linker, it is designed to enable selective drug release in the intracellular environment through cleavage of the disulfide bond. The compound targets TM4SF1 ECL1 for cancer therapy applications. Toxicity studies are conducted on the complete ADC rather than the linker alone. Standard laboratory safety precautions should be followed when handling this compound.
|
| References |
[1]. Fang J,New target for treating cancer. WO2019015696A2.
|
| Additional Infomation |
PDP-Pfp is a reducible ADC linker targeting the extracellular loop 1 (ECL1) of TM4SF1, with molecular formula C14H8F5NO2S2. The compound features a perfluorophenyl ester and a pyridyl disulfide group, enabling conjugation to targeting agents and selective intracellular drug release. It is primarily used in the synthesis of antibody-drug conjugates for cancer research. The linker is designed to maintain stability in circulation while enabling drug release in the reducing intracellular environment. PDP-Pfp is for research use only and has not been approved for clinical applications. Storage at 2-8°C is recommended.
|
| Molecular Formula |
C14H8NO2F5S2
|
|---|---|
| Molecular Weight |
381.34082
|
| Exact Mass |
380.991
|
| CAS # |
160580-70-1
|
| PubChem CID |
10474947
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.6
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
24
|
| Complexity |
407
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=NC(=C1)SSCCC(=O)OC2=C(C(=C(C(=C2F)F)F)F)F
|
| InChi Key |
ICRMTRFPJXTUCG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H8F5NO2S2/c15-9-10(16)12(18)14(13(19)11(9)17)22-8(21)4-6-23-24-7-3-1-2-5-20-7/h1-3,5H,4,6H2
|
| Chemical Name |
(2,3,4,5,6-pentafluorophenyl) 3-(pyridin-2-yldisulfanyl)propanoate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 100 mg/mL (262.23 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.56 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 25.0 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: ≥ 2.5 mg/mL (6.56 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6223 mL | 13.1117 mL | 26.2233 mL | |
| 5 mM | 0.5245 mL | 2.6223 mL | 5.2447 mL | |
| 10 mM | 0.2622 mL | 1.3112 mL | 2.6223 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
