[CAS NO. 863971-53-3] Fmoc-Val-Cit-PAB-PNP
PRODUCTS SPECIFICATIONS [863971-53-3]
DESCRIPTION [863971-53-3]
Overview
| MDL | MFCD22200278 |
|---|---|
| Molecular Weight | 766.80 |
| Molecular Formula | C40H42N6O10 |
| SMILES | CC(C)[C@@H](C(N[C@@H](CCCNC(N)=O)C(NC1=CC=C(COC(OC2=CC=C([N+]([O-])=O)C=C2)=O)C=C1)=O)=O)NC(OCC3C4=C(C5=C3C=CC=C5)C=CC=C4)=O |
Summary
Fmoc-Val-Cit-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs) . Fmoc-Val-Cit-PAB-PNP has superior plasma stability comparable to that of non-cleavable linkers [1] [2] [3] .
IC50 & Target
|
Protease Cleavable |
Cleavable |
In Vitro
Fmoc-Val-Cit-PAB-PNP contains peptide sequence degradable by a lysosome enzyme
[1]
.
Cathepsin B in the lysosome cleaves the peptide bond between Cit-PAB of dipeptide linkers containing Valine (Val)-citrulline (Cit) and p-aminobenzylalcohol (PAB). When PAB and a drug are binded covalently with carbamate bonds, the drug can be released by hydrolysis after cleavage of the peptide bond between Cit-PAB. Antibody-drug conjugates (ADCs) has been developed using this mechanism
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Fmoc-Val-Cit-PAB-PNP linker stabilization in the mouse is an essential prerequisite for designing successful efficacy and safety studies in rodents during preclinical stages of ADC programs
[3]
.
Conjugation site plays an important role in determining VC-PABC linker stability in mouse plasma, and that the stability of the linker positively correlates with ADC cytotoxic potency both in vitro and in vivo
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
DMSO : ≥ 40 mg/mL ( 52.16 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 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 |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 5.25 mg/mL (6.85 mM); Clear solution
References
- [1] Dubowchik GM, et al. Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: model studies of enzymatic drug release and antigen-specific in vitro anticancer activity. Bioconjug Chem. 2002 Jul-Aug;13(4):855-69.
- [2] Yoneda Y, et al. A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy. Bioorg Med Chem Lett. 2008 Mar 1;18(5):1632-6.
- [3] Dorywalska M, et al. Effect of attachment site on stability of cleavable antibody drug conjugates. Bioconjug Chem. 2015 Apr 15;26(4):650-9.
