The PPAR Ω Pocket: Renewed Opportunities for Drug Development.

Abstract:

:The past decade of PPARγ research has dramatically improved our understanding of the structural and mechanistic bases for the diverging physiological effects of different classes of PPARγ ligands. The discoveries that lie at the heart of these developments have enabled the design of a new class of PPARγ ligands, capable of isolating central therapeutic effects of PPARγ modulation, while displaying markedly lower toxicities than previous generations of PPARγ ligands. This review examines the emerging framework around the design of these ligands and seeks to unite its principles with the development of new classes of ligands for PPARα and PPARβ/δ. The focus is on the relationships between the binding modes of ligands, their influence on PPAR posttranslational modifications, and gene expression patterns. Specifically, we encourage the design and study of ligands that primarily bind to the Ω pockets of PPARα and PPARβ/δ. In support of this development, we highlight already reported ligands that if studied in the context of this new framework may further our understanding of the gene programs regulated by PPARα and PPARβ/δ. Moreover, recently developed pharmacological tools that can be utilized in the search for ligands with new binding modes are also presented.

journal_name

PPAR Res

journal_title

PPAR research

authors

Kaupang Å,Hansen TV

doi

10.1155/2020/9657380

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

9657380

eissn

1687-4757

issn

1687-4765

journal_volume

2020

pub_type

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