Discovery of a Novel Cabazitaxel Nanoparticle-Drug Conjugate (CRLX522) with Improved Pharmacokinetic Properties and Anticancer Effects Using a β-Cyclodextrin-PEG Copolymer Based Delivery Platform.
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:
14 11 2019
14 11 2019
Historique:
pubmed:
9
10
2019
medline:
17
6
2020
entrez:
9
10
2019
Statut:
ppublish
Résumé
Novel nanoparticle-drug conjugates (NDCs) containing diverse, clinically relevant anticancer drug payloads (docetaxel, cabazitaxel, and gemcitabine) were successfully generated and tested in drug discovery studies. The NDCs utilized structurally varied linkers that attached the drug payloads to a β-cyclodextrin-PEG copolymer to form self-assembled nanoparticles. In vitro release studies revealed a diversity of release rates driven by linker structure-activity relationships (SARs). Improved in vivo pharmacokinetics (PK) for the cabazitaxel (CBTX) NDCs with glycinate-containing (
Identifiants
pubmed: 31593466
doi: 10.1021/acs.jmedchem.9b00892
doi:
Substances chimiques
Antineoplastic Agents
0
Drug Carriers
0
Taxoids
0
beta-Cyclodextrins
0
Polyethylene Glycols
3WJQ0SDW1A
cabazitaxel
51F690397J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM