Info
Trends in Antiviral Drug Development
| Trends in Antiviral Drug Development |
| Autore | Sofia Michael J |
| Edizione | [1st ed.] |
| Pubbl/distr/stampa | Newark : , : John Wiley & Sons, Incorporated, , 2025 |
| Descrizione fisica | 1 online resource (531 pages) |
| Altri autori (Persone) |
WangZhengqiang
FischerJános KleinChristian ChildersWayne E RotellaDavid P |
| Collana | Trends in Drug Discovery Series |
| ISBN |
3-527-84509-7
3-527-84510-0 3-527-84508-9 |
| Formato | Materiale a stampa  |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Cover -- Half Title Page -- Title Page -- Copyright -- Contents -- Preface -- Introduction: Successes and Challenges in Antiviral Drug Development -- Introduction -- Antiviral Drugs Targeting Human Herpesviruses -- Antiviral Drugs Targeting Human Immunodeficiency Virus -- Drugs Targeting Reverse Transcriptase -- Drugs Targeting Protease -- Drugs Targeting Integrase Strand Transfer -- Drugs Targeting Viral Entry -- Drugs Targeting Viral Capsid -- Antiviral Drugs Targeting Hepatitis B Virus -- Antiviral Drugs Targeting Hepatitis Delta Virus -- Antiviral Drugs Targeting Hepatitis C Virus -- Antiviral Drugs Targeting Acute RNA Respiratory Viruses -- Drugs Targeting Human Influenza Viruses -- Drugs Targeting SARS-CoV-2 -- New Trends and Challenges in Antiviral Drug Development -- References -- Part I: Human Herpes Viruses -- Chapter 1: Letermovir for the Prevention of CMV Infection in Transplant Recipients -- 1.1 Background -- 1.1.1 Cytomegalovirus -- 1.1.2 Immunocompromised Patients -- 1.1.3 Patient Groups with a High Risk for CMV Complications -- 1.1.4 Available CMV Treatments Before Letermovir -- 1.1.4.1 Antiviral Drugs -- 1.1.4.2 Dominant Treatment Strategies -- 1.1.4.3 Unmet Medical Need -- 1.2 Discovery Phase -- 1.3 Preclinical Characterization -- 1.3.1 Antiviral Potency/Selectivity/Inhibitory Profile -- 1.3.1.1 In Vitro Potency Versus Laboratory CMV Strains -- 1.3.1.2 In Vitro Potency Versus Clinical CMV Isolates and Resistance-breaking Profile -- 1.3.1.3 In Vivo Efficacy (Xenotransplant Model) -- 1.3.1.4 In Vitro Antiviral Specificity -- 1.3.1.5 Other Characteristics of Letermovir's Inhibitory Profile -- 1.3.1.6 Summary -- 1.4 Mechanism of Action Studies -- 1.4.1 Target Identification -- 1.5 Terminase Inhibitors -- 1.5.1 Previous and Contemporary Drug Candidates Targeting the Terminase Complex.
1.5.2 Letermovir: Same Target, Different Interaction -- 1.5.3 Advantages of Terminase Inhibitors -- 1.6 Preclinical Safety Evaluation -- 1.7 Clinical Development and MAA/NDA Submission -- 1.7.1 Regulatory Support for Clinical Development -- 1.7.2 Phase 1 -- 1.7.2.1 Drug-Drug Interaction Studies -- 1.7.2.2 Special Populations -- 1.7.2.3 IV Formulation -- 1.7.3 Clinical Proof-of-concept -- 1.7.3.1 Phase 2a Clinical Trial (AIC001-2-001) -- 1.7.3.2 Emergency IND Treatment of a Lung Transplant Patient with Multiresistant CMV Disease -- 1.7.3.3 Credentials Established -- 1.7.4 Letermovir for CMV Prophylaxis in HSCT Patients -- 1.7.4.1 Phase 2b: First Prophylaxis Trial in HSCT Patients -- 1.7.4.2 Phase 3 CMV Prophylaxis Trial in HSCT Patients -- 1.7.4.3 Marketing Approval in HSCT Recipients -- 1.7.4.4 Further Clinical Development and Real-world Data -- 1.7.4.4.1 Phase 3 Trial for Extension of the Prophylaxis Period -- 1.7.4.4.2 Follow-up Trials in Specific Populations -- 1.7.5 Letermovir for CMV Prophylaxis in KT Patients -- 1.7.5.1 Phase 3 Noninferiority Trial in KT Recipients -- 1.7.5.2 Marketing Approval in KT Recipients -- 1.7.5.3 Further Clinical Development and Real-world Data -- 1.8 Drug Resistance -- 1.8.1 Genetic Characterization of Letermovir Resistance -- 1.9 Letermovir Resistance in Clinical Trials -- 1.10 Real-world Resistance -- 1.11 Outlook for Letermovir -- Acknowledgments -- References -- Chapter 2: Discovery and Development of the Helicase-Primase Inhibitor Pritelivir for the Treatment of Immunocompromised Patients with Resistant HSV Infection -- 2.1 HSV Virology and Disease -- 2.2 Treatment -- 2.3 Resistant Infections -- 2.4 Pritelivir Discovery and Target Identification -- 2.5 Nonclinical Data -- 2.5.1 In Vitro Studies -- 2.5.2 In Vivo Studies -- 2.5.2.1 Guinea Pig Model for Genital HSV-2 Infection -- 2.5.2.2 Mouse Model for HSE. 2.5.2.3 Pritelivir in Immunocompromised Mouse Model -- 2.6 Clinical Data -- 2.6.1 Phase 1 Program -- 2.6.2 Genital HSV -- 2.6.3 Resistant Infections -- 2.7 Pritelivir Resistance -- 2.8 Conclusion and Outlook -- References -- Part II: Immunodeficiency Virus -- Chapter 3: The Discovery and Early Development of the HIV-1 Integrase Strand Transfer Inhibitor Dolutegravir (S/GSK1349572) -- 3.1 Introduction -- 3.2 Medicinal Chemistry -- 3.2.1 Discovery of S/GSK1349572 (DTG) -- 3.2.1.1 Evolution of the Chemical Structure Leading to DTG -- 3.3 Virology -- 3.3.1 In Vitro Studies Indicated Robust Efficacy and High Barrier to Resistance of DTG -- 3.4 Clinical Development -- 3.4.1 PK Studies Supported Once-daily 50 mg Dosing of DTG -- 3.4.2 Clinical Studies in People Living with HIV-1 -- 3.4.3 Clinical Studies in Individuals with Prior Treatment Failure -- Acknowledgments -- References -- Chapter 4: The Discovery and Development of Islatravir (4'-Ethynyl-2-fluoro-2'-deoxyadenosine [EFdA], MK-8591) -- 4.1 Introduction -- 4.2 HIV Replication Cycle -- 4.3 Structure and Function of HIV RT -- 4.4 DNA Synthesis by RT -- 4.5 RT Inhibitor Classes -- 4.6 EFdA Development -- 4.6.1 4'-Ethynyl Ribose Modifications -- 4.6.2 2-Fluoro Adenosine Modifications -- 4.6.3 3'-Hydroxy Ribose Modification -- 4.7 EFdA: A Compound with 4'-Ethynyl, 2-Fluoro, and 3'-Hydroxy Modifications -- 4.7.1 Effects of the 4'-Ethynyl Modification on EFdA -- 4.7.2 Effects of the 2'-Fluoro Modification on EFdA -- 4.7.3 Effects of the 3'-Hydroxy Modification on EFdA -- 4.7.3.1 Mechanisms of Inhibition: EFdA -- 4.7.3.1.1 Biochemical Mechanisms of Inhibition -- 4.7.3.1.2 Structural Mechanisms of Inhibition -- 4.8 Mechanism of Resistance/Hypersusceptibility to EFdA -- 4.8.1 Mechanisms of Viral Resistance to EFdA -- 4.8.2 Mechanisms of Viral Hypersusceptibility to EFdA. 4.8.3 Combination Therapies with EFdA -- 4.8.4 Synthesis Advances -- 4.9 Animal Studies -- 4.9.1 EFdA Pharmacokinetic Studies in Rodents -- 4.9.2 EFdA Antiviral Activity in Humanized Mice -- 4.9.3 EFdA Antiviral Activity in Rhesus Macaques -- 4.9.4 EFdA Long-acting Activity in Various Animals -- 4.10 Clinical Trials -- 4.11 Long-acting Methods of Delivery for EFdA Treatment -- 4.12 NRTTIs as a Drug Class -- References -- Part III: Hepatitis Viruses -- Chapter 5: Discovery of the RNA Interference Therapeutic Imdusiran, a GalNAc-conjugated siRNA -- 5.1 Introduction -- 5.2 Comparison of Preclinical Anti-HBV Efficacy Between Lipid Nanoparticle-encapsulated and GalNAc-conjugated siRNA -- 5.3 Comparison of Tetravalent Versus Trivalent GalNAc Ligands -- 5.4 siRNA Selection: Comparison of siRNA Activity Against HBsAg and HBx Targets -- 5.5 Imdusiran Design and Preclinical Characterization -- 5.5.1 Abrogation of siRNA Immunostimulatory Potential -- 5.5.2 Imdusiran siRNA Target Site Sequence -- 5.6 Imdusiran Antiviral Activity -- 5.6.1 Imdusiran Antiviral Activity in Primary Mouse and Human Hepatocyte HBV Models -- 5.6.2 Imdusiran In Vivo Antiviral Activity -- 5.7 Imdusiran Combination Treatment -- 5.7.1 Imdusiran Combination with Standard of Care and Investigational Agents -- 5.8 Perspectives -- References -- Chapter 6: Discovery and Development of ARO-HBV/JNJ-3989 -- 6.1 Introduction -- 6.1.1 Chronic Hepatitis B Virus Infection -- 6.1.1.1 HBV Structure and Associated Molecular and Cellular Biology -- 6.1.1.1.1 Clinical Course of HBV Infection -- 6.2 Development of RNAi Therapeutic ARO-HBV/JNJ-73763989 (JNJ-3989) -- 6.2.1 RNAi as a Therapeutic Modality -- 6.2.2 Use of siRNA to Treat HBV Infection -- 6.2.2.1 JNJ-3989 siRNAs Have Broad Cross-reactivity to HBV Genotypes and HBV Transcripts. 6.2.2.1.1 Reduction of Serum HBsAg, HBeAg, and HBV DNA in Mouse Model of Chronic HBV Infection -- 6.3 Pharmacokinetics and Safety of JNJ-3989 in Humans -- 6.4 Clinical Studies in Chronically HBV-infected Patients -- 6.4.1 Direct Antiviral Treatment Approach with JNJ-3989-based Regimens -- 6.4.1.1 Pharmacological Response to JNJ-3989 with Short-term Treatment -- 6.4.1.2 REEF-1 Clinical Study -- 6.4.1.3 REEF-2 Clinical Study -- 6.4.2 Combination Approaches of JNJ-3989 with Immune Modulation -- 6.4.2.1 PENGUIN Clinical Study -- 6.4.2.2 REEF-IT Clinical Study -- 6.4.3 HBsAg Targeting siRNA JNJ-3989 in Chronic Hepatitis D -- 6.4.3.1 REEF-D Clinical Study -- 6.5 Discussion and Perspectives -- References -- Chapter 7: The Discovery and Development of Sofosbuvir as the Backbone of HCV Curative Therapies -- 7.1 Introduction -- 7.2 Identification of the 2'- -F, 2'-ß-C-Methyl Cytidine Nucleoside PSI-6130 -- 7.3 Identification of the 3',5'-Diisobutyrate Ester Prodrug RG7128 and Clinical Proof-of-concept -- 7.4 Development of the 5'-Phosphoramidate Uridine Nucleotide Prodrug for Liver Targeting and Clinical Proof-of-concept -- 7.5 Sofosbuvir: The Backbone of HCV Curative Therapies -- 7.6 Conclusion -- References -- Chapter 8: The Discovery and Development of Harvoni® and Epclusa®: Ending the Interferon Era -- Curing All Hepatitis C Genotypes -- 8.1 Cure -- 8.2 Introduction -- 8.3 The Discovery of Ledipasvir [13-15] -- 8.4 Early Development of Ledipasvir -- 8.5 Ledipasvir/Sofosbuvir STR Clinical Trial Results and Real-world Effectiveness -- 8.6 Initiation of a Pangenotypic NS5A Inhibitor Program -- 8.7 Discovery of the Pangenotypic NS5A Inhibitor Velpatasvir [40-42] -- 8.8 The Development of Velpatasvir -- 8.9 Clinical Trial Efficacy and Real-world Effectiveness with the Pangenotypic Sofosbuvir/Velpatasvir STR -- 8.10 Conclusion -- Acknowledgment. Compliance with Ethical Standards. |
| Record Nr. | UNINA-9911019658503321 |
Sofia Michael J
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| Newark : , : John Wiley & Sons, Incorporated, , 2025 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
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Trends in CNS Drug Discovery
| Trends in CNS Drug Discovery |
| Autore | Doller Dario |
| Edizione | [1st ed.] |
| Pubbl/distr/stampa | Newark : , : John Wiley & Sons, Incorporated, , 2025 |
| Descrizione fisica | 1 online resource (483 pages) |
| Altri autori (Persone) |
HodgettsKevin J
FischerJános KleinChristian ChildersWayne E RotellaDavid P |
| Collana | Trends in Drug Discovery Series |
| ISBN |
3-527-84468-6
3-527-84467-8 3-527-84469-4 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Cover -- Title Page -- Copyright -- Contents -- Series Editors Preface -- Preface -- Chapter 1 CNS Drug Discovery in "The Century of Biology" -- 1.1 Welcome to "The Century of Biology"! -- 1.2 Understanding Brain Health Around the World -- 1.3 Where Are New CNS Drugs Coming from? -- 1.4 Psychedelics as Potential Therapeutic Drugs -- 1.5 CNS Drugs Acting at Novel Biological Targets -- 1.6 Starting with the End in Mind: Defining a CNS Disease -- 1.7 Where to Go from Here -- References -- Chapter 2 Advances in Disease Modifying Therapies for Parkinson's Disease -- 2.1 Introduction -- 2.2 Parkinson's Disease Pathology -- 2.2.1 Protein Aggregation and Propagation -- 2.2.2 Genetics of Parkinson's Disease -- 2.3 Disease‐Modifying Treatments for Parkinson's Disease -- 2.3.1 α‐Synuclein Targeting -- 2.3.1.1 Immunization -- 2.3.1.2 Reducing α‐Synuclein Expression -- 2.3.1.3 Inhibition of α‐Synuclein Aggregation -- 2.3.1.4 Enhancing Clearance and Degradation of α‐Synuclein -- 2.3.2 Targeting Non‐receptor Tyrosine Kinases c‐Abl -- 2.3.3 Glucocerebrosidase Targeting -- 2.3.4 Leucine‐Rich Repeat Kinase 2 Targeting -- 2.3.5 Targeting Other Players -- 2.3.5.1 Targeting Glucagon‐like Peptide‐1 -- 2.3.5.2 Anti‐Apoptotic and Antioxidant Agents -- 2.3.5.3 Myeloperoxidase Inhibitors -- 2.3.5.4 Targeting of α‐Syn Post‐Translational Modifications -- 2.4 Progress and Challenges -- References -- Chapter 3 Psychedelics‐Inspired Drug Discovery -- 3.1 Introduction -- 3.2 What Are Psychedelics and What Makes a Compound, Psychedelic? -- 3.3 What Is Known about the Therapeutic Mechanism of Action of Psychedelics? -- 3.4 Typical Psychedelics -- 3.4.1 The Receptors -- 3.4.2 The Compounds -- 3.5 Non‐psychedelic Serotonergic Agonists -- 3.6 Atypical Psychedelics -- 3.6.1 κ‐Opioid Receptor (KOR) Agonists Act as Dissociatives.
3.6.2 N‐Methyl‐D‐Aspartate Receptor (NMDA) Antagonists Are Dissociative Anesthetics -- 3.6.3 γ‐Aminobutyric Acid (GABAA) Receptor Agonists Are Hypnotic Dissociatives -- 3.6.4 Muscarinic Acetylcholine Receptor (mAChR Aka Cholinergic Receptor) Antagonists May Act as Deliriants -- 3.7 Psychoactive Cannabinoids as Atypical Psychedelics -- 3.7.1 What Are Cannabinoids? -- 3.7.2 Cannabinoids as Therapeutics -- 3.7.3 Current and Future Cannabinoid Research -- 3.8 Conclusion -- References -- Chapter 4 Epilepsy and Related Seizure Disorders -- 4.1 Introduction -- 4.1.1 What Is a Seizure? -- 4.1.2 Epilepsy -- 4.1.2.1 Definition -- 4.1.2.2 Classification -- 4.1.3 Medical Management Strategies for Epilepsy -- 4.1.3.1 Present Medical Management in Clinical Practice -- 4.1.3.2 Initiation and Monitoring of ASM -- 4.1.3.3 Patient Response to Anti‐Seizure Medication -- 4.2 Models and Mechanisms of Drug‐Resistant Epilepsy -- 4.2.1 In Vitro Models of Drug‐Resistant Epilepsy -- 4.2.1.1 Low Magnesium Extracellular Concentrations -- 4.2.1.2 4‐Aminopyridine -- 4.2.1.3 Mimicking Additional Components Contributing to Pharmacoresistance -- 4.2.1.4 Patient‐Derived Embryonic and Induced Pluripotent Stem Cells -- 4.2.2 In Vivo Models of Drug‐Resistant Epilepsy -- 4.2.3 Proposed Mechanisms of Drug Resistance -- 4.3 Targets for Drug Development -- 4.3.1 History of Epilepsy Drug Development -- 4.3.2 Mechanisms of Action in Novel Drug Targets under Investigation -- 4.3.2.1 Modulators of Voltage‐Gated Sodium Channels -- 4.3.2.2 Reduction of T‐Type Voltage‐Gated Calcium Channel Activity -- 4.3.2.3 Activators of Voltage‐Gated Potassium Channels -- 4.3.2.4 Modulation of Neurotransmission -- 4.3.2.5 Regulation of Synaptic Vesicle Proteins -- 4.3.2.6 Targeting the Immune System -- 4.3.2.7 Gene Therapy -- 4.3.2.8 Epigenetic Modification -- 4.3.2.9 Modulators of Synaptic Plasticity. 4.3.2.10 Other -- 4.4 Future Challenges in Epilepsy Drug Development -- Acknowledgments: -- References -- Chapter 5 Strategies for Neuroprotection in Alzheimer's Disease -- 5.1 Introduction -- 5.2 Targeting Pathogenic Protein Aggregation -- 5.2.1 Aβ -- 5.2.1.1 Immunotherapy Against Aβ -- 5.2.1.2 Aβ Cleavage -- 5.2.2 Tau -- 5.2.2.1 Immunotherapy Against Tau -- 5.2.2.2 Gene Therapies -- 5.2.2.3 Modulation of Tau Post‐translation Modifications -- 5.2.2.4 Microtubule Stabilization -- 5.3 Oxidative Stress and Mitochondrial Dysfunction -- 5.4 Neuroinflammation -- 5.5 Protein Processing Pathways -- 5.5.1 Autophagy -- 5.6 Conclusions -- References -- Chapter 6 Rigor in Experimental Design in Nonregulated Preclinical Research in Neuroscience Drug Discovery -- 6.1 Introduction -- 6.2 What Makes Data Robust? -- 6.2.1 Experimental Design Features to Improve Internal Validity -- 6.2.1.1 Randomization -- 6.2.1.2 Blinding -- 6.2.1.3 Exclusion Criteria -- 6.2.1.4 Sex as a Biological Variable (SABV) -- 6.3 Other Types of Validity and Poor Translatability -- 6.4 Threats to Robust Data -- 6.4.1 Underpowered Studies -- 6.4.2 Questionable Research Practices -- 6.4.3 Reporting Bias -- 6.4.4 Lack of Preregistration -- 6.4.5 Research Misconduct -- 6.5 Reporting Standards -- 6.6 Animal Welfare -- 6.7 Regulated Versus Nonregulated Nonclinical Studies -- 6.7.1 GLP Studies -- 6.7.2 Non‐GxP Studies -- 6.8 Conclusion -- References -- Chapter 7 Biomarkers in CNS Drug Discovery, Drug Development, and Clinical Implementation -- 7.1 Introduction -- 7.2 Biomarkers in Drug Discovery, Development, and Clinical Implementation -- 7.2.1 Biomarker Types and Applications -- 7.2.2 Life Cycle of a Biomarker: From Preclinical Discovery to Clinical Development -- 7.2.2.1 Preclinical Biomarker Discovery -- 7.2.2.2 Biomarkers in Clinical Trials. 7.2.2.3 The Importance of Validation and Qualification -- 7.3 Biomarkers for Alzheimer's Disease: History and Overview -- 7.3.1 History and Progress in Diagnostic Biomarkers for AD -- 7.3.2 Use of Diagnostic and Potential Surrogate Biomarkers to Facilitate Regulatory Approval for AD -- 7.4 Pharmacodynamic and Candidate Surrogate Biomarkers for AD -- 7.4.1 Core AD Biomarkers: Aβ and Tau -- 7.4.2 The Importance of Biomarkers of Synaptic Health and Function -- 7.4.3 Established Synaptic Biomarkers -- 7.4.4 Exploratory Synaptic Biomarkers -- 7.4.5 Inflammation‐Related Biomarkers -- 7.4.6 Biomarkers of Vascular Dysfunction -- 7.5 Discovering New Biomarkers for AD: An Ongoing Need -- 7.5.1 Identifying New Biomarkers Through Discovery Proteomics -- 7.6 Case Study: Example of Successful Discovery of New Candidate Biomarkers Through Proteomics in the SHINE‐A Clinical Cohort -- 7.6.1 SHINE‐A Use of Biomarkers to Demonstrate Target or Pathway Engagement in a Clinical Trial -- 7.6.2 SHINE‐A Use of Surrogate Biomarkers of Disease Modification -- 7.7 Advancements in Biomarker Discovery and Development for Neurodegenerative Diseases Beyond AD -- 7.8 Conclusions and Future Directions -- References -- Chapter 8 Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) in CNS Drug Discovery -- 8.1 Introduction -- 8.1.1 PET Imaging in Drug Discovery -- 8.1.2 The Early Drug Discovery Situation -- 8.2 PET Imaging in Clinical Drug Development -- 8.2.1 Proof of Distribution (PoD) -- 8.2.2 Proof of Occupancy (PoO) -- 8.2.2.1 Designing Target Occupancy Studies -- 8.2.2.2 Quantifying Target Occupancy -- 8.2.3 Proof of Mechanism (PoM) -- 8.2.3.1 Magnetic Resonance Imaging (MRI) and Hybrid PET/MRI -- 8.3 PET Radioligand Discovery and Development -- 8.3.1 Considerations Before Initiating a CNS PET Radioligand Discovery Project. 8.3.2 Small Molecule CNS PET Radioligand Design Parameters -- 8.3.3 PET Radioligand Stage‐Gates from Hits to Clinical PET Radioligand -- 8.3.3.1 Hit‐Finding Phase: Radioligand Hits -- 8.3.3.2 Hit‐to‐Lead Phase: Radioligand Leads -- 8.3.3.3 Lead Optimization Phase: Preclinical Radioligand -- 8.3.3.4 Clinical PET Radioligand Candidate -- 8.3.3.5 Clinical PET Radioligand -- 8.3.4 Emerging Application of Immuno‐PET for CNS Imaging -- 8.4 Conclusion -- References -- Chapter 9 Bioanalytical Strategies to De‐risk CNS Drug Discovery for Novel Chemical Modalities -- 9.1 Introduction -- 9.2 Permeation of Molecules into the Brain: Key Compartments and Processes -- 9.3 Key Considerations for Novel Chemical and Biological Constructs -- 9.4 A Brief History of the Kp,uu Concept and Its Importance for CNS‐Focused Drug Design -- 9.5 Moving Beyond the Rule‐of‐5 and Newer Territory for CNS Drugs -- 9.6 Understanding Analytical Errors and Variability in Brain Penetration Measurements -- 9.7 Potential Bioanalytical Technologies for Novel Modalities -- 9.8 Bioanalytical Approaches to Account for Brain Concentration and Brain Vascular Volume -- 9.9 Measuring Target Engagement -- 9.10 Summary and Conclusions -- References -- Chapter 10 Discovery of ABBV‐951 (VYALEV™/PRODUODOPA®) for Advanced Parkinson's Disease -- 10.1 Introduction -- 10.2 Synthesis of Levodopa and Carbidopa Phosphate Prodrugs -- 10.2.1 Levodopa‐4′‐monophosphate (Foslevodopa) Synthesis -- 10.2.2 Carbidopa‐4′‐monophosphate (Foscarbidopa) Synthesis -- 10.3 Preclinical Characterization -- 10.3.1 Solubility and Stability -- 10.3.2 Bioconversion -- 10.3.3 Preclinical Safety -- 10.4 Clinical First‐in‐Human and Phase 1 Studies -- 10.4.1 First‐in‐human ABBV‐951 Study -- 10.4.2 First in Patient ABBV‐951 Study -- 10.5 Conclusions -- References. Chapter 11 Inducers of Targeted Protein Degradation as Drug Candidates for Neurodegenerative Disorders. |
| Record Nr. | UNINA-9911020110203321 |
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Doller Dario
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| Newark : , : John Wiley & Sons, Incorporated, , 2025 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
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Trends in MRNA Vaccine Research
| Trends in MRNA Vaccine Research |
| Autore | Szabo Gabor Tamas |
| Edizione | [1st ed.] |
| Pubbl/distr/stampa | Newark : , : John Wiley & Sons, Incorporated, , 2025 |
| Descrizione fisica | 1 online resource (428 pages) |
| Altri autori (Persone) |
PardiNorbert
FischerJános KleinChristian ChildersWayne E |
| Collana | Trends in Drug Discovery Series |
| Soggetto topico |
COVID-19 vaccines
Messenger RNA |
| ISBN |
9783527838387
3527838384 9783527838394 3527838392 9783527838370 3527838376 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto | Cover -- Title Page -- Copyright -- Contents -- Preface -- Preface from the Volume Editors -- Part I How mRNA Vaccines Work -- Chapter 1 A Historical Overview on mRNA Vaccine Development -- 1.1 Introduction -- 1.2 The Path of mRNA as an Unstable and Toxic Product to a New Class of Medicine -- 1.2.1 The Discovery and In Vitro Production of mRNA -- 1.2.2 The Inflammatory Nature of mRNA -- 1.3 How Studying Lipid Bilayer Structures in Cell Membranes Gave Rise to the Eventual Development of Lipid Nanoparticles for RNA Delivery -- 1.3.1 From Biological Cell Membranes to Liposomal Drugs -- 1.3.2 Ionizable Lipid Nanoparticles for Systemic Delivery of Nucleic Acids -- 1.4 The Journey of Developing Clinical mRNA Vaccines -- 1.5 Concluding Remarks -- References -- Chapter 2 Immune Responses to mRNA Vaccine -- 2.1 Introduction -- 2.2 Innate Sensing of RNA Molecules -- 2.3 Innate Immune Response to mRNA Vaccines -- 2.3.1 Innate Immune Response in Humans -- 2.3.2 Tissue Innate Immune Response in Mice -- 2.4 mRNA Design and Innate Immunity -- 2.4.1 Cap -- 2.4.2 Untranslated Regions -- 2.4.3 Poly(A) -- 2.4.4 Coding Sequence -- 2.5 Optimization and Production of mRNA for an Adequate Innate Immune Response |
| Record Nr. | UNINA-9911019785503321 |
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Szabo Gabor Tamas
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| Newark : , : John Wiley & Sons, Incorporated, , 2025 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
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