Identification and Optimization of EphA2-Selective Bicycles for the Delivery of Cytotoxic Payloads.
Amino Acid Sequence
Animals
Bridged Bicyclo Compounds, Heterocyclic
/ administration & dosage
Cytotoxins
/ administration & dosage
Drug Delivery Systems
/ methods
Ephrin-A2
/ antagonists & inhibitors
Female
Humans
Liver
/ diagnostic imaging
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Protein Structure, Secondary
Protein Structure, Tertiary
Receptor, EphA2
Xenograft Model Antitumor Assays
/ methods
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:
23 04 2020
23 04 2020
Historique:
pubmed:
24
3
2020
medline:
25
9
2020
entrez:
24
3
2020
Statut:
ppublish
Résumé
Bicycles are constrained bicyclic peptides that represent a promising binding modality for use in targeted drug conjugates. A phage display screen against EphA2, a receptor tyrosine kinase highly expressed in a number of solid tumors, identified a number of Bicycle families with low nanomolar affinity. A Bicycle toxin conjugate (BTC) was generated by derivatization of one of these Bicycles with the potent cytotoxin DM1 via a cleavable linker. This BTC demonstrated potent antitumor activity
Identifiants
pubmed: 32202781
doi: 10.1021/acs.jmedchem.9b02129
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Cytotoxins
0
EPHA2 protein, human
0
Ephrin-A2
0
Receptor, EphA2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM