TY - JOUR
T1 - Unexpected emergence of luciferase-inhibitory activity during structural development study of phenyloxadiazole-based PPAR ligands
AU - Shioi, Ryuta
AU - Toyota, Yosuke
AU - Noguchi-Yachide, Tomomi
AU - Ishikawa, Minoru
AU - Yamaguchi, Takao
AU - Makishima, Makoto
AU - Hashimoto, Yuichi
AU - Ohgane, Kenji
N1 - Funding Information:
The work described in this article was supported in part by Grant-in-Aid for Scientific Research (Grant-in-Aid for Young Scientists B, Grant number 17K15487).
Publisher Copyright:
© 2018 The Japan Institute of Heterocyclic Chemistry
PY - 2018
Y1 - 2018
N2 - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate transcription of genes involved in lipid, glucose, and cholesterol homeostasis in a ligand-dependent manner. PPARs have long been a target of drug development, and evaluation of PPARs activity frequently involves reporter-gene assay, in which luciferase activity is utilized to visualize transcriptional activation by the receptors. Here, we report our experience of the unexpected emergence of luciferase-inhibitory activity during our search for PPAR antagonists. We believe information about negative experiences like this will help to make medicinal chemists more aware of potential pitfalls in SAR studies with luciferase-based assays.
AB - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate transcription of genes involved in lipid, glucose, and cholesterol homeostasis in a ligand-dependent manner. PPARs have long been a target of drug development, and evaluation of PPARs activity frequently involves reporter-gene assay, in which luciferase activity is utilized to visualize transcriptional activation by the receptors. Here, we report our experience of the unexpected emergence of luciferase-inhibitory activity during our search for PPAR antagonists. We believe information about negative experiences like this will help to make medicinal chemists more aware of potential pitfalls in SAR studies with luciferase-based assays.
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U2 - 10.3987/COM-18-S(T)61
DO - 10.3987/COM-18-S(T)61
M3 - Article
AN - SCOPUS:85064526139
VL - 97
SP - 854
EP - 864
JO - Heterocycles
JF - Heterocycles
SN - 0385-5414
IS - 2
ER -