40 Years of Duocarmycins: A Graphical Structure/Function Review o Their Chemical Evolution, from SAR to Prodrugs and ADCs

Felber, Jan G. und Thorn-Seshold, Oliver (2022): 40 Years of Duocarmycins: A Graphical Structure/Function Review o Their Chemical Evolution, from SAR to Prodrugs and ADCs. In: JACS Au, Bd. 2, Nr. 12: S. 2636-2644

Abstract

Synthetic analogues of the DNA-alkylating cytotoxins of the duocarmycin class have been extensively investigated in the past 40 years, driven by their high potency, their unusual mechanism of bioactivity, and the beautiful modularity of their structure-activity relationship (SAR). This Perspective analyzes how the molecular designs of synthetic duocarmycins have evolved: from (1) early SAR studies, through to modem applications for directed cancer therapy as (2) prodrugs and (3) antibody-drug conjugates in late-stage clinical development. Analyzing 583 primary research articles and patents from 1978 to 2022, we distill out a searchable A0-format Millard map poster of ca. 200 key structure/function-tuning steps tracing chemical developments across these three key areas. This structure-based overview showcases the ingenious approaches to tune and target bioactivity, that continue to drive development of the elegant and powerful duocarmycin platform.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• Sprache: Englisch