Chapter 10: Enhancing the Polarity of the Linker-drug in ADCs

This chapter describes the advances made in the field of enhancement of polarity of linker-drugs and the application thereof in the field of ADC research with a particular focus on clinical-stage ADCs. While the topics discussed here include the application of polar payloads, polar linkers, and polar capping, the prime focus of this chapter is on polar linkers that span PEG linkers, peptide-based linkers, saccharide-based linkers, sulfur/phosphorus-based linkers, and amine-based linkers. The use of polar linkers is discussed in conjunction with hydrophobic payloads with the objective to generate ADCs retaining the pharmacokinetic profile of native antibodies, as well as having good efficacy.