CHAPTER 16: Pyridinobenzodiazepines (PDDs) as Sequence-selective DNA Mono-alkylating Antibody-Drug Conjugate (ADC) Payloads

Nicolas Veillard, Francesco Cascio, Paul J.M. Jackson, David E. Thurston*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

2 Citations (Scopus)

Abstract

Since the discovery of anthramycin in the early 1960s1 and its subsequent clinical evaluation,2 a range of synthetic pyrrolobenzodiazepines (PBDs)3 have been developed by various groups. For example, the C8-linked PBD dimer tesirine (discussed in Chapter 14) has been incorporated into a number of ADCs currently in clinical development,4 and synthetic mono-alkylating 'pseudodimers' [e.g. the indolinobenzodiazepines (IGNs)5 discussed in Chapter 15] and other types of DNA cross-linkers (e.g., the isoquinolidinobenzodiazepines6) have also been incorporated into pre-clinical and clinical ADC candidates7 (Figure 16.1). However, ADC payload molecules of this type are promiscuous in only having a limited ability to target specific sequences of DNA.

Original languageEnglish
Title of host publicationTherapies for Retinal Degeneration
Subtitle of host publicationTargeting Common Processes
EditorsDavid E. Thurston, Paul J. M. Jackson
PublisherRoyal Society of Chemistry
Pages349-363
Number of pages15
Edition71
DOIs
Publication statusPublished - 1 Jan 2019

Publication series

NameRSC Drug Discovery Series
Number71
Volume2019-January
ISSN (Print)2041-3203
ISSN (Electronic)2041-3211

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