The stability of the Fmoc-Val-Cit-PAB-PNP linker in mice is deemed crucial for conducting effective efficacy and safety studies in rodent models, serving as a foundational step in the preclinical phase of ADC development programs^[3].

Moreover, the site of conjugation significantly influences the stability of the VC-PABC linker in mouse plasma. There's a positive correlation between the stability of this linker and the cytotoxic potency of the corresponding ADC, both in vitro and in vivo, highlighting the importance of linker design in ADC efficacy^[3].

This linker includes a peptide sequence susceptible to degradation by lysosomal enzymes^[1].

The enzyme Cathepsin B in the lysosome specifically targets and cleaves the peptide bond between Cit-PAB within dipeptide linkers composed of Valine (Val)-citrulline (Cit) and p-aminobenzylalcohol (PAB). This process enables the release of a drug covalently attached to PAB via carbamate bonds, following the peptide bond's cleavage between Cit-PAB, a mechanism exploited in the development of ADCs^[2].