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A screening system for identification of fragment molecules toward creation of nuclear receptor ligands

Peroxisome proliferator-activated receptor (PPAR) is the nuclear receptor-type transcription factor with three cognate subtypes (α, δ, γ) that drastically regulates lipid, glucose and amino acid metabolism. Fibrate-class PPARα agonists are clinically used as lipid (triglyceride)-lowering drugs while thiazolidinedione-class PPARγ agonists as anti-diabetic drugs; PPARδ agonists are expected to be anti-metabolic syndrome drugs that have properties mimicking those of both PPARα and PPARγ agonists. Furthermore, PPAR dual or pan agonists that binds to 2 or 3 PPAR subtypes are currently in worldwide clinical trials that mainly target NASH/NAFLD. PPARs have relatively large ligand binding pockets compared to other nuclear receptors, and accept a wide variety of ligands with various fashions and regulate transcription of multiple gene sets. However, non-transcription regulation-type effects are also reported, which attract further attention as another pharmacological impact. This symposium features five speakers who present PPAR–various ligand structures mainly revealed by X-ray crystallography and drug development based on such information.

Drug development based on PPAR-ligand structural studies

The 142nd Annual Meeting of the Pharmaceutical Society of Japan (Nagoya)

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[S07-2]A screening system for identification of fragment molecules toward creation of nuclear receptor ligands

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