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Article

International Union of Pharmacology. LXVI. Orphan Nuclear Receptors

Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)

Abstract

Introduction

What Are Orphan Receptors?

Biological Functions of Orphan Receptors

Unorthodox LBD for Unorthodox NRs

The Paradox: Toward Pharmacology of Orphan Receptors?

Half of the members of the nuclear receptors superfamily are so-called "orphan" receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.

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