Fmoc-Val-Cit-PAB-PNP 

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].

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.

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.

766.80

Solid

C₄₀H₄₂N₆O₁₀

863971-53-3

Fmoc-V-Cit-PAB-PNP

CC(C)[[email protected]@H](C(N[[email protected]@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

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

• [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]