Systematic Variation of Pyrrolobenzodiazepine (PBD)-Dimer Payload Physicochemical Properties Impacts Efficacy and Tolerability of the Corresponding Antibody-Drug Conjugates.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
10 09 2020
10 09 2020
Historique:
pubmed:
14
8
2020
medline:
15
12
2020
entrez:
14
8
2020
Statut:
ppublish
Résumé
Cytotoxic pyrrolobenzodiazepine (PBD)-dimer molecules are frequently utilized as payloads for antibody-drug conjugates (ADCs), and many examples are currently in clinical development. In order to further explore this ADC payload class, the physicochemical properties of various PBD-dimer molecules were modified by the systematic introduction of acidic and basic moieties into their chemical structures. The impact of these changes on DNA binding, cell membrane permeability, and
Identifiants
pubmed: 32787101
doi: 10.1021/acs.jmedchem.0c00691
doi:
Substances chimiques
Immunoconjugates
0
Pyrroles
0
pyrrolo(2,1-c)(1,4)benzodiazepine
0
Benzodiazepines
12794-10-4
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM