Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies.
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Constitutive Androstane Receptor
Cyclophosphamide
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Lymphoma, Non-Hodgkin
/ drug therapy
Molecular Structure
Prodrugs
/ chemical synthesis
Receptors, Cytoplasmic and Nuclear
/ agonists
Structure-Activity Relationship
Tumor Cells, Cultured
Chemotherapy
Co-culture
Cyclophosphamide
Human constitutive androstane receptor
Structure-activity relationship
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Oct 2019
01 Oct 2019
Historique:
received:
25
04
2019
revised:
10
06
2019
accepted:
11
06
2019
pubmed:
28
6
2019
medline:
5
11
2019
entrez:
28
6
2019
Statut:
ppublish
Résumé
The DNA alkylating prodrug cyclophosphamide (CPA), alone or in combination with other agents, is one of the most commonly used anti-cancer agents. As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Therefore, hCAR agonists represent novel sensitizers for CPA-based therapies. Among known hCAR agonists, compound 6-(4-chlorophenyl)imidazo-[2,1-b]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO) is the most potent and broadly utilized in biological studies. Through structural modification of CITCO, we have developed a novel compound DL5016 (32), which has an EC
Identifiants
pubmed: 31247375
pii: S0223-5234(19)30559-8
doi: 10.1016/j.ejmech.2019.06.031
pmc: PMC6718324
mid: NIHMS1532734
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Constitutive Androstane Receptor
0
Prodrugs
0
Receptors, Cytoplasmic and Nuclear
0
Cyclophosphamide
8N3DW7272P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
84-99Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM107058
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121550
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
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