Exposure time versus cytotoxicity for anticancer agents.
Concentration times time
CxT
Epigenetic agents
NCI60
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
11
02
2019
accepted:
02
05
2019
pubmed:
19
5
2019
medline:
22
4
2020
entrez:
19
5
2019
Statut:
ppublish
Résumé
Time is a critical factor in drug action. The duration of inhibition of the target or residence time of the drug molecule on the target often guides drug scheduling. The effects of time on the concentration-dependent cytotoxicity of approved and investigational agents [300 compounds] were examined in the NCI60 cell line panel in 2D at 2, 3, 7 and in 3D 11 days. There was a moderate positive linear relationship between data from the 2-day NCI60 screen and the 3-, 7- and 11-day and a strong positive linear relationship between 3-, 7- and 11-day luminescence screen IC The results suggest that variations in compound exposure time may reflect either mechanism of action or compound chemical half-life. The activity of slow-acting compounds may optimally be assessed in spheroid models that can be monitored over prolonged incubation times.
Identifiants
pubmed: 31102023
doi: 10.1007/s00280-019-03863-w
pii: 10.1007/s00280-019-03863-w
pmc: PMC8127868
mid: NIHMS1694934
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
359-371Subventions
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC010677
Pays : United States
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