Antiangiogenic Activity and in Silico Cereblon Binding Analysis of Novel Thalidomide Analogs.
Adaptor Proteins, Signal Transducing
/ metabolism
Angiogenesis Inhibitors
/ chemistry
Animals
Aorta
/ drug effects
Computer Simulation
Humans
Male
Molecular Docking Simulation
Neovascularization, Physiologic
/ drug effects
Rats
Rats, Sprague-Dawley
Thalidomide
/ analogs & derivatives
Ubiquitin-Protein Ligases
/ metabolism
angiogenesis
cereblon
docking
structure–activity relationships
thalidomide
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
02 Dec 2020
02 Dec 2020
Historique:
received:
18
09
2020
revised:
25
11
2020
accepted:
27
11
2020
entrez:
5
12
2020
pubmed:
6
12
2020
medline:
10
4
2021
Statut:
epublish
Résumé
Due to its antiangiogenic and anti-immunomodulatory activity, thalidomide continues to be of clinical interest despite its teratogenic actions, and efforts to synthesize safer, clinically active thalidomide analogs are continually underway. In this study, a cohort of 27 chemically diverse thalidomide analogs was evaluated for antiangiogenic activity in an ex vivo rat aorta ring assay. The protein cereblon has been identified as the target for thalidomide, and in silico pharmacophore analysis and molecular docking with a crystal structure of human cereblon were used to investigate the cereblon binding abilities of the thalidomide analogs. The results suggest that not all antiangiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.
Identifiants
pubmed: 33276504
pii: molecules25235683
doi: 10.3390/molecules25235683
pmc: PMC7730988
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Angiogenesis Inhibitors
0
CRBN protein, human
0
Thalidomide
4Z8R6ORS6L
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : ZIA SC006538
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Wellcome Trust
ID : 098252/Z/12/Z
Pays : United Kingdom
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