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Title Nuclear receptors : the art and science of modulator design and discovery / Mostafa Z. Badr, editor
Published Cham, Switzerland : Springer, 2021

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Description 1 online resource
Contents Chapter 5: Structure-Based Design of Estrogen-Related Receptors Modulators -- 5.1 Introduction -- 5.2 Structure and Function -- 5.3 Medicinal Chemistry of ERR Modulators -- 5.3.1 ERR Inverse Agonists -- 5.3.2 ERRs Agonists -- References -- Chapter 6: PPAR[alpha] and Ligand Design: Honing the Traditional Empirical Method with a More Holistic Overview -- 6.1 Introduction to the PPAR Protein -- 6.1.1 Overall PPAR LBD Protein Structure -- 6.1.2 Mechanism of PPAR Gene Transcription -- 6.1.3 Differences in LBD Between PPAR Subtypes -- 6.2 Catalogue of Known Ligands -- 6.2.1 PPAR[alpha] Ligands
Intro -- Preface -- Contents -- About the Editor -- Chapter 1: Molecular Pharmacology of the Youngest Member of the Nuclear Receptor Family: The Mineralocorticoid Receptor -- 1.1 An Overview of the MR Physiology -- 1.2 Evolutionary Profile of the MR -- 1.3 The Hsp90-Based Heterocomplex -- 1.4 MR Trafficking -- 1.5 Agonist Structure-Activity Relationship -- 1.6 MR Antagonism -- 1.7 MR Regulation by Phosphorylation and Redox Potential -- 1.8 Conclusions -- References -- Chapter 2: A Simple Method for Visual Assessment and Quantification of Altered Subcellular Localization of Nuclear Receptors
2.1 Introduction -- 2.2 Materials and Methods -- 2.3 Notes -- References -- Chapter 3: Multifaceted Effects of Ligand on Nuclear Receptor Mobility -- 3.1 Introduction -- 3.2 Nucleocytoplasmic Shuttling of the Nuclear Receptors -- 3.2.1 Nuclear Pore Complexes: Gatekeepers of the Nucleus -- 3.2.2 Nuclear Import Pathways -- 3.2.3 Nuclear Export Pathways -- 3.2.4 Dynamics of Movement Within the Nucleus -- 3.3 Ligand-Dependent Nuclear Accumulation of Nuclear Receptors -- 3.3.1 Glucocorticoid Receptor Nuclear Accumulation and Intranuclear Dynamics -- 3.3.1.1 GR Nuclear Accumulation
3.3.1.2 GR Intranuclear Dynamics -- 3.3.2 Mineralocorticoid Receptor Nuclear Accumulation and Intranuclear Dynamics -- 3.3.2.1 MR Nuclear Accumulation -- 3.3.2.2 MR Intranuclear Dynamics -- 3.3.3 Androgen Receptor Nuclear Accumulation and Intranuclear Dynamics -- 3.3.3.1 Androgen Receptor Nuclear Accumulation -- 3.3.3.2 Androgen Receptor Intranuclear Dynamics -- 3.4 Ligand-Dependent Intranuclear Localization -- 3.5 Ligand-Independent Trafficking -- 3.5.1 Thyroid Hormone Receptor Intracellular Trafficking -- 3.5.2 Retinoic Acid Receptor Intracellular Trafficking
3.6 Retinoid X Receptor and Vitamin D Receptor Intracellular Trafficking: A Bin of Their Own? -- 3.7 Conclusions -- References -- Chapter 4: Chemical Considerations in Discovery of Receptor Modulators -- 4.1 Introduction -- 4.2 Intermolecular Binding Forces Drive Ligand Action -- 4.3 Sterics and Hydrophobicity in Ligand Binding -- 4.4 Stereochemical Considerations -- 4.5 Molecular Dynamics as a Tool for Modulator Design -- 4.6 Case Study: A Holistic Approach to Liver X Receptor Modulator Design -- 4.7 Conclusions -- References
Summary Nuclear receptors are ligand activated transcription factors that control numerous biological functions. Consequently, altering activity of these receptors is proposed, and indeed documented, to affect many physiological and pathological conditions in experimental animals and humans. Thus, nuclear receptors have become a major target in the effort to treat numerous diseases. This book will shed light on and emphasize intricate processes involved in designing as well as discovering physiological and pharmacological modulators of these important proteins. World-renowned scientists will share with the reader their professional expertise and extensive experience acquired through decades working with nuclear receptors. Chapters address the various means and consequences of modulating nuclear receptor activity will be presented and discussed. These modulators cover a wide span of moieties ranging from synthetic chemicals to natural products. In addition, the classification of these chemicals ranges from pan agonists to selective agonists and inverse agonists to antagonists. They also include proteolytic means to obliterate the receptor in the event that modulating its activity through canonical pharmacological agents becomes less effective and/or less desirable due to anticipated or experienced toxicities. Modulation of receptor activity may also take place in the absence of a ligand or through manipulating the structure of the receptor itself by controlling posttranslational events
Notes Includes index
Online resource; title from PDF title page (SpringerLink, viewed October 14, 2021)
Subject Nuclear receptors (Biochemistry)
Receptors, Cytoplasmic and Nuclear
Nuclear receptors (Biochemistry)
Genre/Form Electronic books
Form Electronic book
Author Badr, Mostafa Z., 1950- editor.
ISBN 9783030783150
3030783154