Metabolism of bioconjugate therapeutics: why, when, and how?

Abstract:

:Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker. The linkage of the active component to a carrier molecule enhances the therapeutic window through a targeted delivery and by reducing toxicity. Bioconjugates also possess improved pharmacokinetic properties such as a long half-life, increased stability, and cleavage by intracellular enzymes/environment. However, premature cleavage of the bioconjugates and the resulting metabolites/catabolites may produce undesirable toxic effects and, hence, it is critical to understand cleavage mechanisms, metabolism of bioconjugates, and translatability to human in the discovery stages. This article provides a comprehensive overview of linker cleavage pathways and catabolism/metabolism of antibody-drug conjugates, glycoconjugates, polymer-drug conjugates, lipid-drug conjugates, folate-targeted small molecule-drug conjugates, and drug-drug conjugates.

journal_name

Drug Metab Rev

journal_title

Drug metabolism reviews

authors

Liu H,Bolleddula J,Nichols A,Tang L,Zhao Z,Prakash C

doi

10.1080/03602532.2020.1716784

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

66-124

issue

1

eissn

0360-2532

issn

1097-9883

journal_volume

52

pub_type

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