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[null,null,"Titolo",null,"Nuclear receptors : the art and science of modulator design and discovery / / Mostafa Z. Badr, editor"]
[null,null,"Pubbl/distr/stampa",null,"Cham, Switzerland : , : Springer, , [2021]"]
[{"$nulls":4},"©2021"]
[null,null,"ISBN",null,"3-030-78315-4"]
[null,null,"Descrizione fisica",null,"1 online resource (676 pages)"]
[null,null,"Disciplina",null,"572.8845"]
[null,null,"Soggetti",null,"Nuclear receptors (Biochemistry)"]
[{"$nulls":4},"Receptors nuclears (Bioquímica)"]
[{"$nulls":4},"Llibres electrònics"]
[null,null,"Lingua di pubblicazione",null,"Inglese"]
[null,null,"Formato",null,"Materiale a stampa"]
[null,null,null,"Livello bibliografico","Monografia"]
[null,null,"Nota di contenuto",null,"Intro -- Preface -- Contents -- About the Editor -- Chapter 1: Molecular Pharmacology of the Youngest Member of the Nuclear Receptor Family: The Mineralocorticoid Receptor -- 1.1 An Overview of the MR Physiology -- 1.2 Evolutionary Profile of the MR -- 1.3 The Hsp90-Based Heterocomplex -- 1.4 MR Trafficking -- 1.5 Agonist Structure-Activity Relationship -- 1.6 MR Antagonism -- 1.7 MR Regulation by Phosphorylation and Redox Potential -- 1.8 Conclusions -- References -- Chapter 2: A Simple Method for Visual Assessment and Quantification of Altered Subcellular Localization of Nuclear Receptors -- 2.1 Introduction -- 2.2 Materials and Methods -- 2.3 Notes -- References -- Chapter 3: Multifaceted Effects of Ligand on Nuclear Receptor Mobility -- 3.1 Introduction -- 3.2 Nucleocytoplasmic Shuttling of the Nuclear Receptors -- 3.2.1 Nuclear Pore Complexes: Gatekeepers of the Nucleus -- 3.2.2 Nuclear Import Pathways -- 3.2.3 Nuclear Export Pathways -- 3.2.4 Dynamics of Movement Within the Nucleus -- 3.3 Ligand-Dependent Nuclear Accumulation of Nuclear Receptors -- 3.3.1 Glucocorticoid Receptor Nuclear Accumulation and Intranuclear Dynamics -- 3.3.1.1 GR Nuclear Accumulation -- 3.3.1.2 GR Intranuclear Dynamics -- 3.3.2 Mineralocorticoid Receptor Nuclear Accumulation and Intranuclear Dynamics -- 3.3.2.1 MR Nuclear Accumulation -- 3.3.2.2 MR Intranuclear Dynamics -- 3.3.3 Androgen Receptor Nuclear Accumulation and Intranuclear Dynamics -- 3.3.3.1 Androgen Receptor "]
[{"$nulls":4},"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."]
[{"$nulls":4},"References -- Chapter 4: Chemical Considerations in Discovery of Receptor Modulators -- 4.1 Introduction -- 4.2 Intermolecular Binding Forces Drive Ligand Action -- 4.3 Sterics and Hydrophobicity in Ligand Binding -- 4.4 Stereochemical Considerations -- 4.5 Molecular Dynamics as a Tool for Modulator Design -- 4.6 Case Study: A Holistic Approach to Liver X Receptor Modulator Design -- 4.7 Conclusions -- References -- Chapter 5: Structure-Based Design of Estrogen-Related Receptors Modulators -- 5.1 Introduction -- 5.2 Structure and Function -- 5.3 Medicinal Chemistry of ERR Modulators -- 5.3.1 ERR Inverse Agonists -- 5.3.2 ERRs Agonists -- References -- Chapter 6: PPARα and δ Ligand Design: Honing the Traditional Empirical Method with a More Holistic Overview -- 6.1 Introduction to the PPAR Protein -- 6.1.1 Overall PPAR LBD Protein Structure -- 6.1.2 Mechanism of PPAR Gene Transcription -- 6.1.3 Differences in LBD Between PPAR Subtypes -- 6.2 Catalogue of Known Ligands -- 6.2.1 PPARα Ligands -- 6.2.1.1 PPARα Full Agonists -- WY14643 or Pirinixic Acid -- GW590735/Compound 25a -- Pemafibrate -- 6.2.1.2 PPARα Antagonist -- GW6471 -- 6.2.2 PPARδ Ligands -- 6.2.2.1 PPARδ Full Agonists -- GW2433 -- GW2331 -- LC1765 -- Compound 48 -- Isoquinoline Compound 5 -- TIPP-204 -- GW0742 -- GW501516, Compounds 1-16 -- Compound 18 and Compound 13 -- 6.2.2.2 PPARδ Partial Agonists -- Compound 2 -- GW9371 -- 6.2.3 Dual or Pan Agonist Ligands -- 6.2.3.1 PPARα/γ Dual Agonists -- GW409544 -- Azetidinone Compounds 17 and 35 -- GL479 -- 6.2.3.2 PPARα/δ Dual Agonists -- TIPP-401 -- 6.2.3.3 PPARδ/γ Dual Agonists -- Phenoxyacetic Acid Compounds 10 and 21 -- Sulfonylthiadiazole Compounds 6, 11t and 20a -- 6.2.3.4 Pan Agonists -- Indeglitazar -- TIPP-703 -- AL29-26 -- 6.2.3.5 Endogenous Agonists -- Eicosapentaenoic Acid (20:5 EPA) -- Vaccenic Acid (18:1) -- Iloprost."]
[{"$nulls":4},"17(S)-oxoDHA (22:6) -- 6.3 Ligand Design Factors -- 6.4 Tools and New Information -- 6.4.1 Examples of Computer-Aided Drug Design -- 6.4.2 Pharmacokinetics and Pharmacodynamics -- 6.4.3 Wider Considerations for PPAR -- 6.4.3.1 LBD Mutations -- 6.4.3.2 PPAR Intact Structure and Implications -- 6.4.3.3 Coregulators and FABPs -- 6.5 Conclusion -- References -- Chapter 7: Pregnane X Receptor: Understanding Its Function and Activity at the Molecular Level -- 7.1 Introduction -- 7.2 The Chemical Landscape of PXR Ligands -- 7.3 The Structural Architecture of PXR -- 7.4 Dimerization of PXR -- 7.5 Coregulatory Recruitment to PXR -- 7.6 AF-2 Helix Orientation Dictates PXR's Activation -- 7.7 Ligand Binding Stabilizes the Structure of PXR -- 7.8 Ligand-Binding Site of PXR and Ligand Promiscuity -- 7.9 Species Selectivity in PXR Activation -- 7.10 PXR Inhibitors -- 7.11 PXR Agonists as Therapeutics -- 7.12 Conclusion -- References -- Chapter 8: Strategies for the Design of Vitamin D Receptor Ligands -- 8.1 Introduction -- 8.2 Secosteroid VDR Ligands -- 8.3 Non-secosteroid VDR Ligands -- 8.4 VDR Antagonists -- 8.5 Concluding Remarks and Future Directions -- References -- Chapter 9: What Makes a Good Antagonist: Lessons Learned from the Estrogen and Aryl Hydrocarbon Receptors -- 9.1 Introduction: What Is an Antagonist? -- 9.2 Identification and Development of ER Antagonists -- 9.2.1 A Brief History of the Development of ER Antagonists -- 9.2.2 Molecular Characterization of ERs -- 9.2.3 The Antagonistic Activity of SERMs "]
[{"$nulls":4},"Involves Repositioning of Helix 12 -- 9.2.4 Additional Classes of ERα Antagonists -- 9.3 Development of AHR Antagonists -- 9.3.1 Early Days of AHR Discovery -- 9.3.2 Molecular Structure of the AHR -- 9.3.3 Agonist-Induced Activation of the AHR -- 9.3.4 The AHR Is Activated by a Diverse Cadre of Ligands."]
[{"$nulls":4},"9.3.5 Development of Selective AHR Modulators (SAHRMs) -- 9.3.6 Toward the Development of \"Pure\"  AHR Antagonists -- 9.3.7 Development of Flavone-Based AHR Antagonists -- 9.3.8 Development of Indole-Based AHR Antagonists -- 9.3.9 Development of Stilbene-Based AHR Antagonists -- 9.3.10 Development of AHR-PROTACs (SAHRDs) -- 9.3.11 Elucidating the Rules That Govern Agonist Versus Antagonist-Induced AHR Activity -- 9.4 Conclusions and Future Directions -- References -- Chapter 10: Design of Novel PPAR Agonist for Neurodegenerative Disease -- 10.1 Introduction -- 10.2 Overview of PPARs and Their Structures -- 10.3 PPAR-Gamma Activation Site -- 10.4 Structure of the Ligand-Binding Domain -- 10.5 Structural Dynamics of PPAR Gamma -- 10.6 Selective PPAR Modulators (SPPARMs) -- 10.7 PPAR Delta Active Site Description -- 10.8 PPAR Alpha Active Site Description -- 10.9 PPARS and Neurodegenerative Diseases -- 10.10 PPARS for Alzheimer's Disease: Overview of AD -- 10.11 PPARs and Neuroinflammation -- 10.12 PPARs and Microglia and Neurotrophins -- 10.13 PPARS, TREM2, and Amyloid Beta -- 10.14 Conclusion -- References -- Chapter 11: Functional Bioassays Lithograph Ligand Reflections in the PPARα Sphere -- 11.1 PPARs Are Nuclear Hormone Receptors -- 11.2 The RXR Obligation -- 11.3 Screening for PPAR Activators -- 11.4 Reporter Plasmids of PPAR-RXR Heterodimer Activity -- 11.5 Power of the Imperfect -- 11.6 Is It a Ligand? -- 11.7 Saturation and Competition-Binding Analyses -- 11.8 Ligand-Dependent Conformational Change -- 11.9 Altered DNA-Binding Affinity -- 11.10 Crystal Structure -- 11.11 Summary -- References -- Chapter 12: Computational Applications on Food Contact Chemicals as Nuclear Receptor Binders -- 12.1 Introduction -- 12.2 Methods to Evaluate Food Contaminants as Nuclear Receptor Modulators."]
[{"$nulls":4},"12.3 In Vitro Bioassays to Study the Mechanism of Action (MoA) of Endocrine Disruptor Compounds -- 12.3.1 Ligand-Binding Assays -- 12.3.2 Gene Reporter Assays -- 12.3.3 Steroidogenesis Assay -- 12.4 In Silico Methods for Screening Endocrine Disruptor Compounds -- 12.4.1 3D Protein Structure: The Starting Point of Computational Methods -- 12.4.2 Ligand-Based Virtual Screening -- 12.4.3 Molecular Docking -- 12.4.4 Consensus Scoring -- 12.4.5 Molecular Dynamic Simulations -- 12.5 Case Studies -- References -- Chapter 13: Nuclear Hormone Receptors and Host-Virus Interactions -- 13.1 Introduction -- 13.2 Nuclear Receptor Structure and Function -- 13.3 PPAR Signaling and Host-Virus Interactions -- 13.3.1 PPARs and Hepatitis C Virus (HCV) -- 13.3.2 PPARs and Flaviviruses -- 13.3.3 PPARs and Human Immunodeficiency Virus (HIV) -- 13.3.4 PPARs and Other Examples of Viruses -- 13.3.4.1 Hepatitis B Virus -- 13.3.4.2 Influenza A Viruses (IAVs) -- 13.3.4.3 Herpesviruses -- 13.4 Liver X Receptors (LXRs) and Host-Virus Interactions -- 13.4.1 LXR and HCV -- 13.4.2 HIV-1 and LXR -- 13.4.3 LXR and Other Examples of Viruses -- 13.4.3.1 Influenza A Viruses -- 13.4.3.2 Herpesviruses and LXR -- 13.4.3.3 HBV -- 13.5 FXR and Host-Virus Interactions -- 13.5.1 FXR Signaling -- 13.5.2 FXR Signaling During HCV Infection -- 13.5.3 FXR Signaling During HBV Infection -- 13.6 Conclusions -- References -- Chapter 14: Retinoic Acid-Related Orphan Receptor (ROR) Inverse Agonists: Potential Therapeutic Strategies for Multiple Inflammatory Diseases? -- 14.1 Introduction -- 14.2 Functions of RORs in Immune "]
[{"$nulls":4},"Cells -- 14.3 RORs and Autoimmune Disease -- 14.4 Vitamin D3, VDR, and RORs -- 14.5 Multiple Sclerosis (MS) -- 14.6 Psoriasis -- 14.7 Role of RORα in Cardiac Injury and Heart Failure -- 14.8 RORs in Asthma and Acute Respiratory Distress Syndrome (ARDS) -- 14.9 Rheumatoid Arthritis."]
[{"$nulls":4},"14.10 Sjögren's Syndrome (SS)."]