ZFIN ID: ZDB-PUB-190801-5
Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model
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.
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.
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.
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