PUBLICATION
Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model
- Authors
- Jeong, J., Kim, K.H., Kim, D.Y., Chandrasekaran, G., Kim, M., Pagire, S.H., Dighe, M., Choi, E.Y., Bak, S.M., Kim, E.Y., Shin, M.G., Choi, S.Y., Ahn, J.H.
- ID
- ZDB-PUB-190801-5
- Date
- 2019
- Source
- Bioorganic & Medicinal Chemistry 27(19): 115014 (Journal)
- Registered Authors
- Choi, Seok-Yong
- Keywords
- Antagonist, Aryl hydrocarbon receptor (AhR), Stem cell, Zebrafish
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors*
- COS Cells
- Cell Proliferation/drug effects
- Chalcones/chemical synthesis
- Chalcones/pharmacology*
- Chlorocebus aethiops
- Humans
- Receptors, Aryl Hydrocarbon/antagonists & inhibitors*
- Stem Cells/drug effects
- Zebrafish
- Zebrafish Proteins/antagonists & inhibitors*
- PubMed
- 31358358 Full text @ Bioorg. Med. Chem.
Citation
Jeong, J., Kim, K.H., Kim, D.Y., Chandrasekaran, G., Kim, M., Pagire, S.H., Dighe, M., Choi, E.Y., Bak, S.M., Kim, E.Y., Shin, M.G., Choi, S.Y., Ahn, J.H. (2019) Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model. Bioorganic & Medicinal Chemistry. 27(19):115014.
Abstract
A new series of 1,3-diketone, heterocyclic and α,β-unsaturated derivatives were synthesized and evaluated for their AhR antagonist activity using zebrafish and mammalian cells. Compounds 1b, 2c, 3b and 5b showed significant AhR antagonist activity in a transgenic zebrafish model. Among them, compound 3b, and 5b were found to have excellent AhR antagonist activity with IC50 of 3.36 nM and 8.3 nM in a luciferase reporter gene assay. In stem cell proliferation assay, compound 5b elicited marked HSC expansion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping