Duocarmycin–PBD Dimers as Antibody–Drug Conjugate (ADC) Payloads
Duocarmycin–pyrrolobenzodiazepine (PBD) dimers are DNA minor groove cross-linking agents formed by linking together an alkylating subunit from the duocarmycin and pyrrolobenzodiazepine classes of natural products. This chapter describes the structures of the 14 known examples, along with representative syntheses, and characterisation of the dimers' DNA alkylating ability (sequence selectivity and cross-linking efficiency) and cytotoxicity in a diverse range of tumour cell lines. One particular dimer example, with a relatively simple structure and concentrations giving 50% of maximum inhibition (IC