MC-VAL-CIT-PABC-PNP丨CAS 159857-81-5

MC-VAL-CIT-PABC-PNP is a widely used linker–payload precursor in the development of antibody–drug conjugates (ADCs) and other targeted drug-delivery systems. Its modular structure incorporates a maleimidocaproyl (MC) moiety for site-specific conjugation to cysteine residues on antibodies, the dipeptide Val–Cit which is cleavable by lysosomal cathepsin B, and a para-aminobenzyloxycarbonyl (PABC) self-immolative spacer that enables controlled release of the active drug. The p-nitrophenyl (PNP) leaving group facilitates attachment of various cytotoxic agents or other payloads through nucleophilic substitution. This precursor is used in the synthesis of linker–drug modules designed for targeted cancer therapy, where its enzymatically cleavable motif ensures selective drug release inside tumor cells. It is also applied in research programs exploring prodrugs, targeted small-molecule delivery, and next-generation bioconjugates for therapeutic and diagnostic use.

The compound offers significant advantages due to its highly engineered, modular design. The MC group provides stable and predictable conjugation to antibodies, producing well-defined ADCs with controlled drug-to-antibody ratios. The Val–Cit dipeptide enhances tumor specificity because it is preferentially cleaved in lysosomal environments, improving therapeutic index and reducing systemic toxicity. The PABC spacer ensures efficient self-immolative release of the active payload after enzymatic cleavage, allowing for consistent and high-potency intracellular activation. The PNP ester functionality enables straightforward coupling of diverse payloads, streamlining ADC assembly and facilitating rapid optimization of drug candidates. Altogether, the precursor improves synthetic efficiency, conjugation reliability, and biological performance in targeted drug-delivery systems.