Identification of G protein-coupled receptor 120-selective agonists derived from PPARgamma agonists

Takayoshi Suzuki; Sou-Ichi Igari; Akira Hirasawa; Mie Hata; Masaji Ishiguro; Hiroki Fujieda; Yukihiro Itoh; Tatsuya Hirano; Hidehiko Nakagawa; Michitaka Ogura; Makoto Makishima; Gozoh Tsujimoto; Naoki Miyata

doi:10.1021/jm800970b

Identification of G protein-coupled receptor 120-selective agonists derived from PPARgamma agonists

J Med Chem. 2008 Dec 11;51(23):7640-4. doi: 10.1021/jm800970b.

Authors

Takayoshi Suzuki¹, Sou-Ichi Igari, Akira Hirasawa, Mie Hata, Masaji Ishiguro, Hiroki Fujieda, Yukihiro Itoh, Tatsuya Hirano, Hidehiko Nakagawa, Michitaka Ogura, Makoto Makishima, Gozoh Tsujimoto, Naoki Miyata

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.

PMID: 19007110
DOI: 10.1021/jm800970b

Abstract

A weak, nonselective G protein-coupled receptor 120 (GPR120) agonist 10 was found by screening a series of carboxylic acids derived from the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist 3. Modification based on the homology model of GPR120 led to the first GPR120-selective agonist 12. These results provide a basis for constructing new tools for probing the biology of GPR120 and for developing new candidate therapeutic agents.

MeSH terms

Binding Sites / drug effects
Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry*
Carboxylic Acids / pharmacology*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Design
Humans
Hydrogen Bonding
Models, Molecular
Molecular Structure
PPAR gamma / agonists*
Receptors, G-Protein-Coupled / agonists*
Stereoisomerism
Structure-Activity Relationship

Substances

Carboxylic Acids
FFAR4 protein, human
PPAR gamma
Receptors, G-Protein-Coupled