Identifizierung und Charakterisierung des inversen PPARβ/δ-Agonisten DG172

In den vergangenen Jahren konnten Nachweise erbracht werden, dass PPARβ/δ an einer Vielzahl schwerer Erkrankungen wie Krebs, Atherosklerose und Diabetes mellitus beteiligt ist. Eine mögliche therapeutische Option könnte daher eine Modulation dieses Rezeptors mittels spezifischer inhibitorischer Lig...

Full description

Saved in:
Bibliographic Details
Main Author: Lieber, Sonja
Contributors: Müller, Rolf (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2014
Online Access:PDF Full Text
Tags: Add Tag
No Tags, Be the first to tag this record!

Research of the past years has provided clear evidence that PPARβ/δ is associated with major diseases including cancer, atherosclerosis and diabetes mellitus. Modulation of this receptor by specific inhibitory ligands represents a potential therapeutic option. At the beginning of this work highly affine agonists for PPARβ/δ were available, but all described inhibitory ligands were either not selective, not bioavailable or showed a pharmacologically undesirable, irreversible interaction with PPARβ/δ. To investigate the therapeutic potential of PPARβ/δ ligands the development of new was highly desirable. These include antagonists, which inhibit PPARβ/δ activity by competition with endogenous ligands, and inverse agonists, which actively trigger corepressor recruitment and establishment of an active transcriptional repressor complex.