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Enzymatically Cleavable Linkers for Antibody-Drug Conjugates (ADCs)

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.

cleavage mechanism of Val-Cit-PAB linker


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Advantages

  • Contain Val-Cit sequence degradable by a lysosome enzyme
  • Have superior plasma stability comparable to that of non-cleavable linkers
  • Available for manufacturing with several tens gram scale

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