Kooperativer Bibliotheksverbund

UID:

Format: 1 online resource (582 pages)

Edition: 1st ed.

ISBN: 9780443160141

Series Statement: Drug Discovery Update Series

Note: Front Cover -- BIOCHEMICAL AND MOLECULAR PHARMACOLOGY IN DRUG DISCOVERY -- BIOCHEMICAL AND MOLECULAR PHARMACOLOGY IN DRUG DISCOVERY -- Copyright -- Contents -- Contributors -- I - Biochemical and molecular aspects -- 1 - Structures and functions of biomolecules -- 1. Introduction -- 1.1 About biomolecules -- 1.2 Carbohydrates -- 1.2.1 Structure of carbohydrates -- 1.2.2 Functions of carbohydrates -- 1.3 Proteins -- 1.3.1 Structure of proteins -- 1.3.2 Functions of proteins -- 1.4 Lipids -- 1.4.1 Structure of lipids -- 1.4.2 Functions of lipids -- 1.5 Nucleic acids -- 1.5.1 Structure of nucleic acids -- 1.5.1.1 Types of RNA -- 1.5.2 Functions of nucleic acids -- 2. Structure Activity Relationship (SAR) -- 2.1 Need for the SAR study -- 3. Ligands -- 3.1 Classification of ligands -- 4. Receptors -- 4.1 Classification of receptors -- 4.2 Some of the examples of the receptors acting as therapeutic targets -- 5. Conclusion -- References -- 2 - Pharmacokinetics and pharmacodynamics -- 1. Introduction -- 1.1 Sources of drugs -- 1.2 Drug nomenclature -- 1.3 Drug classification -- 1.4 Drug transport through cell membranes -- 1.4.1 Simple diffusion -- 1.4.2 Filtration -- 1.4.3 Carrier mediated -- 1.4.4 Endocytosis -- 2. Pharmacokinetics (ADME) -- 2.1 Absorption -- 2.1.1 Bioavailability -- 2.1.1.1 Factors affecting oral bioavailability -- 2.1.2 Factors influencing digestive resorption -- 2.1.2.1 Pharmaceutical form -- 2.1.2.2 pH, PKa, log P, molecular weight -- 2.1.2.3 Metabolism in the digestive tract, gastric secretion and food bowl -- 2.1.2.4 First pass effect -- 2.1.2.5 Other factors -- 2.2 Distribution -- 2.2.1 Patterns of distribution -- 2.2.2 Factors affecting distribution of drugs -- 2.2.3 Apparent volume of distribution (Vd) -- 2.3 Metabolism (biotransformation) -- 2.3.1 Site of metabolism -- 2.3.2 Types of metabolic reactions. , 2.3.3 Enzymes responsible for biotransformation -- 2.3.4 Factors affecting hepatic microsomal enzyme activity -- 2.4 Excretion -- 2.4.1 Clearance -- 2.5 Fundamental principles of pharmacokinetics -- 2.5.1 Plasma half-life (t1/2) -- 2.5.2 Loading dose -- 2.5.3 Maintenance dose -- 2.5.4 Methods used to prolong duration of action of drugs -- 3. Pharmacodynamics -- 3.1 Possible mechanisms of action of drugs -- 3.2 Definition of receptors -- 3.3 Affinity -- 3.4 Efficacy -- 3.5 Potency -- 3.6 The amount of response -- 3.7 Relation between concentration and response -- 3.7.1 Dose-response curve of drugs -- 3.7.2 Types of ligands -- 3.7.3 Types of antagonists -- 3.7.4 Non-competitive block types -- 3.7.5 Types of receptors and signal transduction mechanism -- 4. Conclusion -- References -- 3 - Overview of drugs and drug targets -- 1. Introduction -- 1.1 Drug development process -- 1.2 Discovery -- 1.2.1 Target identification and validation -- 1.2.2 Assay development -- 1.2.3 Lead identification -- 1.2.4 Lead optimization -- 1.3 Development -- 1.3.1 Predevelopment -- 1.3.2 Clinical research phase I to III -- 1.3.2.1 Phase I-Human pharmacology -- 1.3.2.2 Phase II-Therapeutic exploratory -- 1.3.2.3 Phase III-Therapeutic confirmatory -- 1.4 Registration -- 1.4.1 Regulatory approval -- 1.4.2 Phase IV-Post marketing -- 2. Drug targets -- 3. Types of drug targets -- 3.1 Common drug targets -- 3.1.1 Species-specific genes as drug targets -- 3.1.2 Nucleic acid as drug targets -- 3.1.3 RNA as drug targets -- 3.1.4 Membranes as drug targets -- 3.1.5 Proteins as drug targets -- 3.1.6 Ligand gated ion channels -- 3.1.7 Nuclear receptors -- 4. Pharmacokinetics and pharmacodynamics -- 4.1 Pharmacokinetics -- 4.1.1 Parameters -- 4.1.2 Absorption -- 4.1.3 Distribution -- 4.1.4 Metabolism -- 4.1.5 Elimination -- 4.1.5.1 Quantitative concepts of elimination. , 4.2 Pharmacodynamics -- 4.2.1 Concepts of pharmacodynamics -- 5. Mechanism of drug actions -- 5.1 Dose-response relationship -- 5.2 Drug action mechanism in anticancer drugs -- 5.2.1 Membrane transport -- 5.2.2 Intracellular activation -- 5.2.3 Drug targets -- 6. Drug interactions -- 6.1 Drug-drug interactions -- 6.2 Drug-food interactions -- 6.3 Drug herb interactions -- 6.4 Drug-disease interaction -- 6.5 Drug-allergy interactions -- 6.6 Drug gene interactions -- 7. Drug delivery system -- 7.1 Lipososmes -- 7.2 Micelles -- 7.3 Gold nanoparticles -- 7.4 Magnetic nanoparticles -- 7.5 Nanospheres -- 7.6 Nanoshells -- 8. Personalized medicine -- 9. Conclusion -- 9.1 Drug ethics consideration -- 9.1.1 Explanation of the purpose of research -- 9.1.2 Explanation of alternatives to research participation -- 9.1.3 Continuous dissemination of pertinent new information -- 9.2 Drug abuse -- References -- 4 - Nucleic acids as drug targets -- 1. Introduction -- 1.1 Background and significance of nucleic acids as drug targets -- 1.2 Purpose and scope of the review -- 2. Types of nucleic acids as drug targets -- 2.1 DNA as a drug target -- 2.2 RNA as a drug target -- 2.2.1 mRNA as a target for gene expression regulation -- 2.2.2 Noncoding RNA as therapeutic targets -- 2.3 Emerging targets: Epigenetic modifications and chromatin remodeling -- 3. Strategies for targeting nucleic acids -- 3.1 Small-molecule drugs that interact with DNA or RNA -- 3.2 Antisense oligonucleotides (ASOs) and RNA interference (RNAi) -- 3.3 CRISPR/Cas9 and gene editing for nucleic acid-targeting -- 4. Nucleic acid targets in disease treatment -- 4.1 Genetic disorders -- 4.1.1 Monogenic disorders -- 4.1.2 Gene editing approaches for hereditary diseases -- 4.2 Viral infections: Targeting viral nucleic acids -- 4.3 Cancer: Targeting oncogenes and tumor suppressor genes. , 5. Challenges in nucleic acid-targeted drug development -- 5.1 Specificity and off-target effects -- 5.2 Delivery and cellular uptake of nucleic acid drugs -- 5.3 Immune response and potential adverse effects -- 5.4 Ethical considerations in gene editing and germline therapy -- 6. Successful nucleic acid-targeted therapies -- 7. Future directions in nucleic acid targeting -- 7.1 Advancements in delivery technologies -- 7.2 Next-generation gene editing tools and precision targeting -- 8. Conclusion -- 8.1 Recapitulation of the importance of nucleic acids as drug targets -- 8.2 Key takeaways and future prospects in nucleic acid-targeted drug development -- References -- 5 - Molecular cloning of drug targets -- 1. Introduction -- 2. Molecular cloning and drugs -- 3. Recombinant DNA technology -- 4. Comparison of the pharmacological profile of "cloned" and "natural" drug target -- 4.1 Some differences in pharmacological profiles between natural and cloned targets -- 5. Molecular cloning of drug targets -- 6. Studies about molecular cloning of drug targets -- 7. Conclusion -- References -- 6 - Pharmacogenetics and pharmacogenomics: Role of pharmacogenomics in drug discovery and development -- 1. Introduction -- 2. Pharmacogenetics and pharmacogenomics-basic concept -- 3. Historical perspective -- 4. Principles of pharmacogenetics and pharmacogenomics -- 5. Pharmacogenomics in the drug discovery and development -- 5.1 Identification and optimization of targets -- 5.2 Drug metabolizing enzymes -- 5.3 Drug transporters -- 5.4 Biomarkers -- 5.5 ADME profile of drug -- 5.6 Drug target polymorphism -- 5.7 Drug resistance -- 5.8 Computational drug designing -- 5.9 Drug repositioning and ADR -- 6. Future implications of pharmacogenomics in drug discovery -- 7. Conclusion -- References -- 7 - Drug receptor interactions -- 1. Introduction. , 2. Physiological, genetic and environmental considerations in pharmacodynamics -- 2.1 Physiological factors -- 2.1.1 Age -- 2.1.2 Sex -- 2.1.3 Pregnancy -- 2.2 Genetic factors -- 2.3 Environmental factors -- 3. Drug receptors -- 3.1 Types of drug receptors -- 3.3 Drug-receptor interaction -- 3.4 Characteristics of drug receptors -- 4. Types of ligands -- 5. Drug-receptor bonds -- 6. Drug receptor affinity and selectivity and resident time -- 7. Specific and nonspecific drug binding -- 8. Pharmacological effects of drug-receptor interactions -- 9. Conclusion -- References -- 8 - Enzymology in drug discovery -- 1. Introduction -- 2. Factors to be considered for prescreening of enzymes -- 2.1 Environmental conditions -- 2.2 Substrate of enzymes -- 2.3 Binding partners -- 2.4 Screening assessment -- 2.5 Kinetics of enzyme -- 3. Postscreening of enzyme citing IC50 -- 3.1 Mechanism of action -- 3.1.1 Counterfeit mechanisms -- 3.2 Slow-binding and tight-binding enzyme inhibition -- 3.3 Various enzymatic forms -- 3.4 Irreversible covalent compounds -- 3.5 Inhibitory mechanism -- 3.6 Analysis of data -- 3.7 Combination of biophysics -- 3.8 Generation of lead from an orthogonal perspective -- 3.9 Combination of binding and catalytic assessment -- 3.9.1 Analysis of reagents -- 3.10 Development of assay -- 3.11 Analysis of hit -- 4. Discussion and conclusion -- References -- 9 - Targeting epitranscriptomics for novel drug development -- 1. Introduction -- 2. RNA modifications: Molecular landscape and functions -- 2.1 The RNA modification spectrum -- 2.2 In-depth examination of RNA modifications -- 2.3 Structural insights into how these modifications influence RNA structure and function -- 2.3.1 Structural insights into RNA modifications -- 2.4 Dynamics of RNA modifications -- 2.4.1 Discussing the reversible and context-dependent nature of RNA modifications. , 2.4.2 Roles of RNA modification writers, erasers, and readers.

Additional Edition: Print version: Rudrapal, Mithun Biochemical and Molecular Pharmacology in Drug Discovery San Diego : Elsevier,c2024 ISBN 9780443160134

Language: English

UID:

Format: 1 online resource (444 pages)

Edition: First edition.

ISBN: 0-443-19201-4

Series Statement: Breaking Tolerance to Antibody-Mediated Immunotherapy Series ; Volume 2

Content: Resistance to Anti-CD20 Antibodies and Approaches for Their Reversal presents in-depth content written by international experts in the study of resistance to anti-CD20 antibodies and approaches for their reversal. Anti-CD20 antibodies are used to achieve B cell depletion and are developed to treat B cell proliferative disorders, including non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. In the past two decades, anti-CD20 antibodies have revolutionized the treatment of all B cell malignancies, however, there are patients that fail to respond to initial therapy or relapse sooner. This book explores new and existing avenues surrounding Anti-CD20 antibodies.

Note: Intro -- Breaking Tolerance to Antibody-Mediated Immunotherapy -- Copyright -- Cover Image Insert -- Aims and Scope of Series ``Breaking Tolerance to Antibody-Targeted Therapies´´ -- About the Series Editor -- Aims and Scope of the Volume -- About the Volume Editor -- Preface -- Contents -- Contributors -- Part I: Therapeutic anti-CD20 antibodies against cancers and escape -- Chapter 1: Therapeutic antibodies against cancer-A step toward the treatment -- Introduction -- Search strategy and selection criteria -- Structural format of therapeutic antibodies and their mechanism -- Designing of chimeric, humanized, and human antibodies -- CD20 as a potential target, the resistance of therapeutic antibody against it, and the importance of computational role -- What do we now know about anti-CD20 and its importance? -- How do cancer cells become resistant to mAbs after receiving treatment? -- Resistance issue with anti-CD20 therapies and potential strategies for reversing their effect -- Computational techniques to design the therapeutic antibody -- Availability of antibody databases -- International Immunogenetics Information System (IMGT) -- Antibodypedia (an examination of antibodies against the human proteome from the perspective of the chromosome) -- TABS (Therapeutic Antibody Database) -- DrugBank -- Thera-SAbDab: The Therapeutic Structural Antibody Database -- Advantages and disadvantages of therapeutic antibodies -- Advantages -- Disadvantages -- Possible side effects -- Current limitations with production cost -- Future -- Predictive biomarkers-A therapeutic response against cancer -- Conclusions -- Acknowledgments -- References -- Chapter 2: Anti-CD20 antibody treatment for B-cell malignancies -- Introduction -- B-cell malignancies -- Diffuse large B-cell lymphoma (DLBCL) -- Follicular lymphoma (FL). , Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) -- Mantle cell lymphoma (MCL) -- Marginal zone lymphomas (MZLs) -- Burkitt lymphoma (BL) -- Lymphoplasmacytic lymphoma (LPL) -- Hairy cell leukemia (HCL) -- Primary large B-cell lymphoma of immune-privileged sites -- Plasma cell myeloma (PCM) -- Mechanism of B-cell carcinogenesis/lymphomagenesis -- BCR signaling and cell survival in B-cell malignancies -- Chromosomal translocations, a survival factor in B-cell malignancies -- Microbial antigens in B-cell malignancies -- DNA repair and B-cell malignancies -- Role of epigenetic mechanisms in B-cell malignancies -- Tumor microenvironment and aging facilitates the progression of carcinogenesis -- Anti-CD20 antibodies -- Mechanism of action of anti-CD20 antibodies -- Efficacy of anti-CD20 antibodies therapy for B-cell malignancies and clinical trials -- Rituximab -- Tositumomab -- Ofatumumab -- Veltuzumab -- Ublituximab -- Side effects and prerequisites related to anti-CD20 antibodies therapy in B-cell malignancies -- Biomarkers for responsive anti-CD20 antibody therapy and solutions for refractory cases -- Future perspectives -- Conclusions -- References -- Chapter 3: Anti-CD20 antibody treatment for diffuse large B cell lymphoma: Genetic alterations and signaling pathways -- Introduction -- Mechanisms of rituximab -- Complement-dependent cytotoxicity -- Antibody-dependent cellular cytotoxicity -- Induction of apoptosis -- Genetic alterations and molecular mechanisms -- Cell signaling -- The NF-κB pathway -- The MAPK pathway and the Ras/Raf/MEK/ERK pathway -- The PI3K/AKT/MTOR pathway -- The JAK-STAT pathway -- BCR signaling -- Fas/FasL apoptotic pathway -- MYC, BCL2, BCL6 -- MYC -- BCL2 -- BCL6 -- Mutations in epigenetically regulated genes -- EZH2 and MLL -- CREBBP and EP300 -- Other frequent gene mutations -- TP53 -- PIM1 -- FOXO1. , Abnormal structure and function of CD20 -- Other possible mechanisms of rituximab resistance -- Immune escape -- B2M gene -- PD-1 and PD-L1 -- Changes in the TME -- Conclusions -- References -- Chapter 4: Non-Hodgkin lymphoma treated with anti-CD20 antibody-based immunochemotherapy -- Introduction -- Clinical experience -- Rituximab -- Follicular lymphoma -- Diffuse large B-cell lymphoma -- Other lymphomas -- Obinutuzumab -- Follicular lymphoma -- Diffuse large B-cell lymphoma -- Other lymphomas -- Ofatumumab -- Anti-CD20xCD3 bispecific antibodies -- Mosunetuzumab -- Glofitamab -- Epcoritamab -- Odronextamab -- Safety of BsAbs -- Anti-CD20 resistance -- Resistance to CDC -- Resistance to ADCC -- Resistance to apoptosis -- Loss of CD20 antigen -- Tumor microenvironment -- New approaches of B-cell-directed therapy: Beyond rituximab -- Type II anti-CD20 antibodies -- CD20xCD3 bispecific antibodies -- Anti-CD20 CAR-Ts -- Conclusions and future perspectives -- References -- Chapter 5: Targeted therapies for follicular lymphoma -- Introduction -- Lenalidomide -- PI3K inhibitors -- BTK inhibitors -- BCL-2 inhibitor -- EZH2 inhibitor -- Antibody-drug conjugates -- Bispecific antibody -- Chimeric antigen receptor T-cell therapy -- Conclusions -- Future perspectives -- Acknowledgments -- References -- Chapter 6: Treatment of relapsed follicular lymphoma -- Background -- Overview of treatment at relapse: Objectives of treatment -- Treatment in challenging situations: POD24 -- Treatment in challenging situations: Histological transformation -- Consolidation of the response: Maintenance -- Consolidation of the response: Stem cell transplantation (SCT) and cellular therapy (CT) -- Conclusions and future perspective -- References -- Chapter 7: New monoclonal antibodies for the treatment of acute lymphoblastic leukemia -- Introduction. , Approved antibody-based therapies for B-ALL -- CD20 and rituximab -- CD19 and blinatumomab -- CD22 and inotuzumab ozogamicin -- Antibody technology and CAR-T cell therapies -- Mechanisms of resistance to licensed antibody therapies -- Antigen alterations as a mechanism of resistance -- Antigen-independent mechanisms of resistance -- The future of licensed antibody-based immunotherapies in ALL -- Investigational therapies -- Novel approaches to existing immunotherapeutic targets for B-ALL -- Novel immunotherapeutic targets in B-ALL -- Antibody approaches to T-ALL -- Conclusions -- Acknowledgment -- References -- Chapter 8: Clinical relevance and therapeutic implications of CD20 expression in Hodgkin's lymphoma -- Introduction -- Etiopathogenesis of classical Hodgkins lymphoma (cHL) and the role of the CD20 marker -- Epstein-Barr virus (EBV) infection and HL -- Classical Hodgkins lymphoma (cHL) -- Pathophysiology -- The role of the tumor microenvironment (TME) and its interactions -- Antibody-dependent cellular cytotoxicity (ADCC) -- Complement-dependent cytotoxicity (CDC) -- Induction of direct cell death -- Impact of the CD20+ expression on the evolution and prognosis of HL -- Standard approach for HL treatment -- Clinical efficacy of anti-CD20 therapy on HL -- Proposed mechanisms of action of anti-CD20 therapy -- CD20, uncertainties, and the rationale for using monoclonal antibodies -- Immunogenicity, safety, and resistance mechanism to anti-CD20 antibodies -- Future perspectives -- Conclusions -- Acknowledgment -- References -- Part II: Resistance and affinity determination of anti-CD20 antibodies -- Chapter 9: Therapeutic options for rituximab-resistant patients -- Introduction -- Mechanisms of rituximab resistance -- Therapeutic options after rituximab resistance. , High-dose chemotherapy (HDT) and radio-immunotherapy (RIT) followed by autologous stem cell transplant (ASCT) -- Type II anti-CD20 mAbs -- Tositumomab -- Obinutuzumab -- Solutions to enhance the ADCC effect of anti-CD20 antibodies -- Second-generation and third-generation anti-CD20 antibodies -- Strategies to enhance the antitumor functions of immune effector cells -- Novel targets for mAbs -- Bispecific antibodies -- Small molecules -- Chimeric antigen receptor T cells (CAR-T) -- Watchful waiting (WW) -- Combination strategies -- Conclusions and perspectives -- Acknowledgments -- References -- Chapter 10: Mechanisms of resistance to anti-CD20 antibodies in lymphoid malignancies -- Introduction -- Factors influencing anti-CD20 mAb activity/resistance -- Pharmacokinetics -- CD20 alterations -- CD20 shaving and internalization -- MS4A1 (CD20 gene) mutations, deletions, and aberrant expression of its splicing variants -- Involvement of transcription factors in MS4A1 gene expression -- Epigenetic dysregulation of CD20 -- Resistance to antibody-dependent cell-mediated cytotoxicity (ADCC) -- Effector cell type -- Fcγ receptor polymorphisms -- Antibody type -- Tumor microenvironment -- Complement-mediated resistance -- Resistance to apoptosis -- Future perspectives -- Conclusions -- Acknowledgment -- References -- Chapter 11: Kinetic exclusion assay using cellular membranes for affinity determination of anti-CD20 antibody -- Anti-CD20 antibodies and biology -- CD20 biology -- Approved antibodies and indications -- Rituximab -- Ofatumumab -- Obinutuzumab -- Type I and Type II antibodies -- Resistance to anti-CD20 antibodies -- Anti-CD20 antibodies and biology summary -- Binding characterization technologies -- Surface plasmon resonance -- Flow cytometry -- KinExA -- Comparison of binding characterization technologies. , Important controls for analytical validity in KinExA experiments.

Additional Edition: Print version: Cho, William Chi Shing Resistance to Anti-CD20 Antibodies and Approaches for Their Reversal San Diego : Elsevier Science & Technology,c2023 ISBN 9780443192005

Language: English

UID:

Format: X, 389 Seiten , Illustrationen , 235 mm x 155 mm

ISBN: 9789048135547

Language: English

Subjects: Medicine

Keywords: Krebs ; Alternative Medizin ; Chinesische Medizin

UID:

Format: XIII, 441 Seiten , Ill. , 235 mm x 155 mm

Edition: 1st ed.

ISBN: 9789400705258 , 9400705255

Series Statement: Evidence-based Anticancer Complementary and Alternative Medicine 1

Note: Text engl.

Language: English

URL: http://deposit.d-nb.de/cgi-bin/dokserv?id=3552187&prov=M&dok_var=1&dok_ext=htm

UID:

Format: XII, 406 Seiten , Ill., graph. Darst.

ISBN: 9789400719828

Series Statement: Evidence-based Anticancer Complementary and Alternative Medicine 2

Note: Text engl.

Language: English

UID:

Format: VIII, 269 Seiten , Ill., graph. Darst. , 235 mm x 155 mm

Edition: 1

ISBN: 9789048126743

Note: Text engl.

Language: English

Keywords: Krebsforschung

UID:

Format: 1 Online-Ressource

ISBN: 9783036522180

Content: Extracellular vesicles (EVs) are particles wrapped in a lipid bilayer membrane and are naturally released from cells. This kind of cargo vessel is a nanostructure that mainly transfers lipids, proteins, various nucleic acid fragments, and metabolic components to neighboring cells or distant parts of the body through the circulatory system. EVs are of great significance to the communication mechanism between cells. This book collects feature articles to enhance our understanding of the biological characteristics of EVs and their potential applications.

Additional Edition: Erscheint auch als Druck-Ausgabe, Hardcover ISBN 978-3-0365-2217-3

Language: English

DOI: 10.3390/books978-3-0365-2218-0

URL: Volltext  (kostenfrei)

URL: Volltext  (kostenfrei)

UID:

Format: 1 online resource (582 pages)

Edition: 1st ed.

ISBN: 9780443160141

Series Statement: Drug Discovery Update Series

Note: Front Cover -- BIOCHEMICAL AND MOLECULAR PHARMACOLOGY IN DRUG DISCOVERY -- BIOCHEMICAL AND MOLECULAR PHARMACOLOGY IN DRUG DISCOVERY -- Copyright -- Contents -- Contributors -- I - Biochemical and molecular aspects -- 1 - Structures and functions of biomolecules -- 1. Introduction -- 1.1 About biomolecules -- 1.2 Carbohydrates -- 1.2.1 Structure of carbohydrates -- 1.2.2 Functions of carbohydrates -- 1.3 Proteins -- 1.3.1 Structure of proteins -- 1.3.2 Functions of proteins -- 1.4 Lipids -- 1.4.1 Structure of lipids -- 1.4.2 Functions of lipids -- 1.5 Nucleic acids -- 1.5.1 Structure of nucleic acids -- 1.5.1.1 Types of RNA -- 1.5.2 Functions of nucleic acids -- 2. Structure Activity Relationship (SAR) -- 2.1 Need for the SAR study -- 3. Ligands -- 3.1 Classification of ligands -- 4. Receptors -- 4.1 Classification of receptors -- 4.2 Some of the examples of the receptors acting as therapeutic targets -- 5. Conclusion -- References -- 2 - Pharmacokinetics and pharmacodynamics -- 1. Introduction -- 1.1 Sources of drugs -- 1.2 Drug nomenclature -- 1.3 Drug classification -- 1.4 Drug transport through cell membranes -- 1.4.1 Simple diffusion -- 1.4.2 Filtration -- 1.4.3 Carrier mediated -- 1.4.4 Endocytosis -- 2. Pharmacokinetics (ADME) -- 2.1 Absorption -- 2.1.1 Bioavailability -- 2.1.1.1 Factors affecting oral bioavailability -- 2.1.2 Factors influencing digestive resorption -- 2.1.2.1 Pharmaceutical form -- 2.1.2.2 pH, PKa, log P, molecular weight -- 2.1.2.3 Metabolism in the digestive tract, gastric secretion and food bowl -- 2.1.2.4 First pass effect -- 2.1.2.5 Other factors -- 2.2 Distribution -- 2.2.1 Patterns of distribution -- 2.2.2 Factors affecting distribution of drugs -- 2.2.3 Apparent volume of distribution (Vd) -- 2.3 Metabolism (biotransformation) -- 2.3.1 Site of metabolism -- 2.3.2 Types of metabolic reactions. , 2.3.3 Enzymes responsible for biotransformation -- 2.3.4 Factors affecting hepatic microsomal enzyme activity -- 2.4 Excretion -- 2.4.1 Clearance -- 2.5 Fundamental principles of pharmacokinetics -- 2.5.1 Plasma half-life (t1/2) -- 2.5.2 Loading dose -- 2.5.3 Maintenance dose -- 2.5.4 Methods used to prolong duration of action of drugs -- 3. Pharmacodynamics -- 3.1 Possible mechanisms of action of drugs -- 3.2 Definition of receptors -- 3.3 Affinity -- 3.4 Efficacy -- 3.5 Potency -- 3.6 The amount of response -- 3.7 Relation between concentration and response -- 3.7.1 Dose-response curve of drugs -- 3.7.2 Types of ligands -- 3.7.3 Types of antagonists -- 3.7.4 Non-competitive block types -- 3.7.5 Types of receptors and signal transduction mechanism -- 4. Conclusion -- References -- 3 - Overview of drugs and drug targets -- 1. Introduction -- 1.1 Drug development process -- 1.2 Discovery -- 1.2.1 Target identification and validation -- 1.2.2 Assay development -- 1.2.3 Lead identification -- 1.2.4 Lead optimization -- 1.3 Development -- 1.3.1 Predevelopment -- 1.3.2 Clinical research phase I to III -- 1.3.2.1 Phase I-Human pharmacology -- 1.3.2.2 Phase II-Therapeutic exploratory -- 1.3.2.3 Phase III-Therapeutic confirmatory -- 1.4 Registration -- 1.4.1 Regulatory approval -- 1.4.2 Phase IV-Post marketing -- 2. Drug targets -- 3. Types of drug targets -- 3.1 Common drug targets -- 3.1.1 Species-specific genes as drug targets -- 3.1.2 Nucleic acid as drug targets -- 3.1.3 RNA as drug targets -- 3.1.4 Membranes as drug targets -- 3.1.5 Proteins as drug targets -- 3.1.6 Ligand gated ion channels -- 3.1.7 Nuclear receptors -- 4. Pharmacokinetics and pharmacodynamics -- 4.1 Pharmacokinetics -- 4.1.1 Parameters -- 4.1.2 Absorption -- 4.1.3 Distribution -- 4.1.4 Metabolism -- 4.1.5 Elimination -- 4.1.5.1 Quantitative concepts of elimination. , 4.2 Pharmacodynamics -- 4.2.1 Concepts of pharmacodynamics -- 5. Mechanism of drug actions -- 5.1 Dose-response relationship -- 5.2 Drug action mechanism in anticancer drugs -- 5.2.1 Membrane transport -- 5.2.2 Intracellular activation -- 5.2.3 Drug targets -- 6. Drug interactions -- 6.1 Drug-drug interactions -- 6.2 Drug-food interactions -- 6.3 Drug herb interactions -- 6.4 Drug-disease interaction -- 6.5 Drug-allergy interactions -- 6.6 Drug gene interactions -- 7. Drug delivery system -- 7.1 Lipososmes -- 7.2 Micelles -- 7.3 Gold nanoparticles -- 7.4 Magnetic nanoparticles -- 7.5 Nanospheres -- 7.6 Nanoshells -- 8. Personalized medicine -- 9. Conclusion -- 9.1 Drug ethics consideration -- 9.1.1 Explanation of the purpose of research -- 9.1.2 Explanation of alternatives to research participation -- 9.1.3 Continuous dissemination of pertinent new information -- 9.2 Drug abuse -- References -- 4 - Nucleic acids as drug targets -- 1. Introduction -- 1.1 Background and significance of nucleic acids as drug targets -- 1.2 Purpose and scope of the review -- 2. Types of nucleic acids as drug targets -- 2.1 DNA as a drug target -- 2.2 RNA as a drug target -- 2.2.1 mRNA as a target for gene expression regulation -- 2.2.2 Noncoding RNA as therapeutic targets -- 2.3 Emerging targets: Epigenetic modifications and chromatin remodeling -- 3. Strategies for targeting nucleic acids -- 3.1 Small-molecule drugs that interact with DNA or RNA -- 3.2 Antisense oligonucleotides (ASOs) and RNA interference (RNAi) -- 3.3 CRISPR/Cas9 and gene editing for nucleic acid-targeting -- 4. Nucleic acid targets in disease treatment -- 4.1 Genetic disorders -- 4.1.1 Monogenic disorders -- 4.1.2 Gene editing approaches for hereditary diseases -- 4.2 Viral infections: Targeting viral nucleic acids -- 4.3 Cancer: Targeting oncogenes and tumor suppressor genes. , 5. Challenges in nucleic acid-targeted drug development -- 5.1 Specificity and off-target effects -- 5.2 Delivery and cellular uptake of nucleic acid drugs -- 5.3 Immune response and potential adverse effects -- 5.4 Ethical considerations in gene editing and germline therapy -- 6. Successful nucleic acid-targeted therapies -- 7. Future directions in nucleic acid targeting -- 7.1 Advancements in delivery technologies -- 7.2 Next-generation gene editing tools and precision targeting -- 8. Conclusion -- 8.1 Recapitulation of the importance of nucleic acids as drug targets -- 8.2 Key takeaways and future prospects in nucleic acid-targeted drug development -- References -- 5 - Molecular cloning of drug targets -- 1. Introduction -- 2. Molecular cloning and drugs -- 3. Recombinant DNA technology -- 4. Comparison of the pharmacological profile of "cloned" and "natural" drug target -- 4.1 Some differences in pharmacological profiles between natural and cloned targets -- 5. Molecular cloning of drug targets -- 6. Studies about molecular cloning of drug targets -- 7. Conclusion -- References -- 6 - Pharmacogenetics and pharmacogenomics: Role of pharmacogenomics in drug discovery and development -- 1. Introduction -- 2. Pharmacogenetics and pharmacogenomics-basic concept -- 3. Historical perspective -- 4. Principles of pharmacogenetics and pharmacogenomics -- 5. Pharmacogenomics in the drug discovery and development -- 5.1 Identification and optimization of targets -- 5.2 Drug metabolizing enzymes -- 5.3 Drug transporters -- 5.4 Biomarkers -- 5.5 ADME profile of drug -- 5.6 Drug target polymorphism -- 5.7 Drug resistance -- 5.8 Computational drug designing -- 5.9 Drug repositioning and ADR -- 6. Future implications of pharmacogenomics in drug discovery -- 7. Conclusion -- References -- 7 - Drug receptor interactions -- 1. Introduction. , 2. Physiological, genetic and environmental considerations in pharmacodynamics -- 2.1 Physiological factors -- 2.1.1 Age -- 2.1.2 Sex -- 2.1.3 Pregnancy -- 2.2 Genetic factors -- 2.3 Environmental factors -- 3. Drug receptors -- 3.1 Types of drug receptors -- 3.3 Drug-receptor interaction -- 3.4 Characteristics of drug receptors -- 4. Types of ligands -- 5. Drug-receptor bonds -- 6. Drug receptor affinity and selectivity and resident time -- 7. Specific and nonspecific drug binding -- 8. Pharmacological effects of drug-receptor interactions -- 9. Conclusion -- References -- 8 - Enzymology in drug discovery -- 1. Introduction -- 2. Factors to be considered for prescreening of enzymes -- 2.1 Environmental conditions -- 2.2 Substrate of enzymes -- 2.3 Binding partners -- 2.4 Screening assessment -- 2.5 Kinetics of enzyme -- 3. Postscreening of enzyme citing IC50 -- 3.1 Mechanism of action -- 3.1.1 Counterfeit mechanisms -- 3.2 Slow-binding and tight-binding enzyme inhibition -- 3.3 Various enzymatic forms -- 3.4 Irreversible covalent compounds -- 3.5 Inhibitory mechanism -- 3.6 Analysis of data -- 3.7 Combination of biophysics -- 3.8 Generation of lead from an orthogonal perspective -- 3.9 Combination of binding and catalytic assessment -- 3.9.1 Analysis of reagents -- 3.10 Development of assay -- 3.11 Analysis of hit -- 4. Discussion and conclusion -- References -- 9 - Targeting epitranscriptomics for novel drug development -- 1. Introduction -- 2. RNA modifications: Molecular landscape and functions -- 2.1 The RNA modification spectrum -- 2.2 In-depth examination of RNA modifications -- 2.3 Structural insights into how these modifications influence RNA structure and function -- 2.3.1 Structural insights into RNA modifications -- 2.4 Dynamics of RNA modifications -- 2.4.1 Discussing the reversible and context-dependent nature of RNA modifications. , 2.4.2 Roles of RNA modification writers, erasers, and readers.

Additional Edition: Print version: Rudrapal, Mithun Biochemical and Molecular Pharmacology in Drug Discovery San Diego : Elsevier,c2024 ISBN 9780443160134

Language: English

UID:

Format: 1 online resource (582 pages)

Edition: 1st ed.

ISBN: 9780443160141

Series Statement: Drug Discovery Update Series

Note: Front Cover -- BIOCHEMICAL AND MOLECULAR PHARMACOLOGY IN DRUG DISCOVERY -- BIOCHEMICAL AND MOLECULAR PHARMACOLOGY IN DRUG DISCOVERY -- Copyright -- Contents -- Contributors -- I - Biochemical and molecular aspects -- 1 - Structures and functions of biomolecules -- 1. Introduction -- 1.1 About biomolecules -- 1.2 Carbohydrates -- 1.2.1 Structure of carbohydrates -- 1.2.2 Functions of carbohydrates -- 1.3 Proteins -- 1.3.1 Structure of proteins -- 1.3.2 Functions of proteins -- 1.4 Lipids -- 1.4.1 Structure of lipids -- 1.4.2 Functions of lipids -- 1.5 Nucleic acids -- 1.5.1 Structure of nucleic acids -- 1.5.1.1 Types of RNA -- 1.5.2 Functions of nucleic acids -- 2. Structure Activity Relationship (SAR) -- 2.1 Need for the SAR study -- 3. Ligands -- 3.1 Classification of ligands -- 4. Receptors -- 4.1 Classification of receptors -- 4.2 Some of the examples of the receptors acting as therapeutic targets -- 5. Conclusion -- References -- 2 - Pharmacokinetics and pharmacodynamics -- 1. Introduction -- 1.1 Sources of drugs -- 1.2 Drug nomenclature -- 1.3 Drug classification -- 1.4 Drug transport through cell membranes -- 1.4.1 Simple diffusion -- 1.4.2 Filtration -- 1.4.3 Carrier mediated -- 1.4.4 Endocytosis -- 2. Pharmacokinetics (ADME) -- 2.1 Absorption -- 2.1.1 Bioavailability -- 2.1.1.1 Factors affecting oral bioavailability -- 2.1.2 Factors influencing digestive resorption -- 2.1.2.1 Pharmaceutical form -- 2.1.2.2 pH, PKa, log P, molecular weight -- 2.1.2.3 Metabolism in the digestive tract, gastric secretion and food bowl -- 2.1.2.4 First pass effect -- 2.1.2.5 Other factors -- 2.2 Distribution -- 2.2.1 Patterns of distribution -- 2.2.2 Factors affecting distribution of drugs -- 2.2.3 Apparent volume of distribution (Vd) -- 2.3 Metabolism (biotransformation) -- 2.3.1 Site of metabolism -- 2.3.2 Types of metabolic reactions. , 2.3.3 Enzymes responsible for biotransformation -- 2.3.4 Factors affecting hepatic microsomal enzyme activity -- 2.4 Excretion -- 2.4.1 Clearance -- 2.5 Fundamental principles of pharmacokinetics -- 2.5.1 Plasma half-life (t1/2) -- 2.5.2 Loading dose -- 2.5.3 Maintenance dose -- 2.5.4 Methods used to prolong duration of action of drugs -- 3. Pharmacodynamics -- 3.1 Possible mechanisms of action of drugs -- 3.2 Definition of receptors -- 3.3 Affinity -- 3.4 Efficacy -- 3.5 Potency -- 3.6 The amount of response -- 3.7 Relation between concentration and response -- 3.7.1 Dose-response curve of drugs -- 3.7.2 Types of ligands -- 3.7.3 Types of antagonists -- 3.7.4 Non-competitive block types -- 3.7.5 Types of receptors and signal transduction mechanism -- 4. Conclusion -- References -- 3 - Overview of drugs and drug targets -- 1. Introduction -- 1.1 Drug development process -- 1.2 Discovery -- 1.2.1 Target identification and validation -- 1.2.2 Assay development -- 1.2.3 Lead identification -- 1.2.4 Lead optimization -- 1.3 Development -- 1.3.1 Predevelopment -- 1.3.2 Clinical research phase I to III -- 1.3.2.1 Phase I-Human pharmacology -- 1.3.2.2 Phase II-Therapeutic exploratory -- 1.3.2.3 Phase III-Therapeutic confirmatory -- 1.4 Registration -- 1.4.1 Regulatory approval -- 1.4.2 Phase IV-Post marketing -- 2. Drug targets -- 3. Types of drug targets -- 3.1 Common drug targets -- 3.1.1 Species-specific genes as drug targets -- 3.1.2 Nucleic acid as drug targets -- 3.1.3 RNA as drug targets -- 3.1.4 Membranes as drug targets -- 3.1.5 Proteins as drug targets -- 3.1.6 Ligand gated ion channels -- 3.1.7 Nuclear receptors -- 4. Pharmacokinetics and pharmacodynamics -- 4.1 Pharmacokinetics -- 4.1.1 Parameters -- 4.1.2 Absorption -- 4.1.3 Distribution -- 4.1.4 Metabolism -- 4.1.5 Elimination -- 4.1.5.1 Quantitative concepts of elimination. , 4.2 Pharmacodynamics -- 4.2.1 Concepts of pharmacodynamics -- 5. Mechanism of drug actions -- 5.1 Dose-response relationship -- 5.2 Drug action mechanism in anticancer drugs -- 5.2.1 Membrane transport -- 5.2.2 Intracellular activation -- 5.2.3 Drug targets -- 6. Drug interactions -- 6.1 Drug-drug interactions -- 6.2 Drug-food interactions -- 6.3 Drug herb interactions -- 6.4 Drug-disease interaction -- 6.5 Drug-allergy interactions -- 6.6 Drug gene interactions -- 7. Drug delivery system -- 7.1 Lipososmes -- 7.2 Micelles -- 7.3 Gold nanoparticles -- 7.4 Magnetic nanoparticles -- 7.5 Nanospheres -- 7.6 Nanoshells -- 8. Personalized medicine -- 9. Conclusion -- 9.1 Drug ethics consideration -- 9.1.1 Explanation of the purpose of research -- 9.1.2 Explanation of alternatives to research participation -- 9.1.3 Continuous dissemination of pertinent new information -- 9.2 Drug abuse -- References -- 4 - Nucleic acids as drug targets -- 1. Introduction -- 1.1 Background and significance of nucleic acids as drug targets -- 1.2 Purpose and scope of the review -- 2. Types of nucleic acids as drug targets -- 2.1 DNA as a drug target -- 2.2 RNA as a drug target -- 2.2.1 mRNA as a target for gene expression regulation -- 2.2.2 Noncoding RNA as therapeutic targets -- 2.3 Emerging targets: Epigenetic modifications and chromatin remodeling -- 3. Strategies for targeting nucleic acids -- 3.1 Small-molecule drugs that interact with DNA or RNA -- 3.2 Antisense oligonucleotides (ASOs) and RNA interference (RNAi) -- 3.3 CRISPR/Cas9 and gene editing for nucleic acid-targeting -- 4. Nucleic acid targets in disease treatment -- 4.1 Genetic disorders -- 4.1.1 Monogenic disorders -- 4.1.2 Gene editing approaches for hereditary diseases -- 4.2 Viral infections: Targeting viral nucleic acids -- 4.3 Cancer: Targeting oncogenes and tumor suppressor genes. , 5. Challenges in nucleic acid-targeted drug development -- 5.1 Specificity and off-target effects -- 5.2 Delivery and cellular uptake of nucleic acid drugs -- 5.3 Immune response and potential adverse effects -- 5.4 Ethical considerations in gene editing and germline therapy -- 6. Successful nucleic acid-targeted therapies -- 7. Future directions in nucleic acid targeting -- 7.1 Advancements in delivery technologies -- 7.2 Next-generation gene editing tools and precision targeting -- 8. Conclusion -- 8.1 Recapitulation of the importance of nucleic acids as drug targets -- 8.2 Key takeaways and future prospects in nucleic acid-targeted drug development -- References -- 5 - Molecular cloning of drug targets -- 1. Introduction -- 2. Molecular cloning and drugs -- 3. Recombinant DNA technology -- 4. Comparison of the pharmacological profile of "cloned" and "natural" drug target -- 4.1 Some differences in pharmacological profiles between natural and cloned targets -- 5. Molecular cloning of drug targets -- 6. Studies about molecular cloning of drug targets -- 7. Conclusion -- References -- 6 - Pharmacogenetics and pharmacogenomics: Role of pharmacogenomics in drug discovery and development -- 1. Introduction -- 2. Pharmacogenetics and pharmacogenomics-basic concept -- 3. Historical perspective -- 4. Principles of pharmacogenetics and pharmacogenomics -- 5. Pharmacogenomics in the drug discovery and development -- 5.1 Identification and optimization of targets -- 5.2 Drug metabolizing enzymes -- 5.3 Drug transporters -- 5.4 Biomarkers -- 5.5 ADME profile of drug -- 5.6 Drug target polymorphism -- 5.7 Drug resistance -- 5.8 Computational drug designing -- 5.9 Drug repositioning and ADR -- 6. Future implications of pharmacogenomics in drug discovery -- 7. Conclusion -- References -- 7 - Drug receptor interactions -- 1. Introduction. , 2. Physiological, genetic and environmental considerations in pharmacodynamics -- 2.1 Physiological factors -- 2.1.1 Age -- 2.1.2 Sex -- 2.1.3 Pregnancy -- 2.2 Genetic factors -- 2.3 Environmental factors -- 3. Drug receptors -- 3.1 Types of drug receptors -- 3.3 Drug-receptor interaction -- 3.4 Characteristics of drug receptors -- 4. Types of ligands -- 5. Drug-receptor bonds -- 6. Drug receptor affinity and selectivity and resident time -- 7. Specific and nonspecific drug binding -- 8. Pharmacological effects of drug-receptor interactions -- 9. Conclusion -- References -- 8 - Enzymology in drug discovery -- 1. Introduction -- 2. Factors to be considered for prescreening of enzymes -- 2.1 Environmental conditions -- 2.2 Substrate of enzymes -- 2.3 Binding partners -- 2.4 Screening assessment -- 2.5 Kinetics of enzyme -- 3. Postscreening of enzyme citing IC50 -- 3.1 Mechanism of action -- 3.1.1 Counterfeit mechanisms -- 3.2 Slow-binding and tight-binding enzyme inhibition -- 3.3 Various enzymatic forms -- 3.4 Irreversible covalent compounds -- 3.5 Inhibitory mechanism -- 3.6 Analysis of data -- 3.7 Combination of biophysics -- 3.8 Generation of lead from an orthogonal perspective -- 3.9 Combination of binding and catalytic assessment -- 3.9.1 Analysis of reagents -- 3.10 Development of assay -- 3.11 Analysis of hit -- 4. Discussion and conclusion -- References -- 9 - Targeting epitranscriptomics for novel drug development -- 1. Introduction -- 2. RNA modifications: Molecular landscape and functions -- 2.1 The RNA modification spectrum -- 2.2 In-depth examination of RNA modifications -- 2.3 Structural insights into how these modifications influence RNA structure and function -- 2.3.1 Structural insights into RNA modifications -- 2.4 Dynamics of RNA modifications -- 2.4.1 Discussing the reversible and context-dependent nature of RNA modifications. , 2.4.2 Roles of RNA modification writers, erasers, and readers.

Additional Edition: Print version: Rudrapal, Mithun Biochemical and Molecular Pharmacology in Drug Discovery San Diego : Elsevier,c2024 ISBN 9780443160134

Language: English

UID:

Format: 1 online resource (444 pages)

Edition: First edition.

ISBN: 0-443-19201-4

Series Statement: Breaking Tolerance to Antibody-Mediated Immunotherapy Series ; Volume 2

Content: Resistance to Anti-CD20 Antibodies and Approaches for Their Reversal presents in-depth content written by international experts in the study of resistance to anti-CD20 antibodies and approaches for their reversal. Anti-CD20 antibodies are used to achieve B cell depletion and are developed to treat B cell proliferative disorders, including non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. In the past two decades, anti-CD20 antibodies have revolutionized the treatment of all B cell malignancies, however, there are patients that fail to respond to initial therapy or relapse sooner. This book explores new and existing avenues surrounding Anti-CD20 antibodies.

Note: Intro -- Breaking Tolerance to Antibody-Mediated Immunotherapy -- Copyright -- Cover Image Insert -- Aims and Scope of Series ``Breaking Tolerance to Antibody-Targeted Therapies´´ -- About the Series Editor -- Aims and Scope of the Volume -- About the Volume Editor -- Preface -- Contents -- Contributors -- Part I: Therapeutic anti-CD20 antibodies against cancers and escape -- Chapter 1: Therapeutic antibodies against cancer-A step toward the treatment -- Introduction -- Search strategy and selection criteria -- Structural format of therapeutic antibodies and their mechanism -- Designing of chimeric, humanized, and human antibodies -- CD20 as a potential target, the resistance of therapeutic antibody against it, and the importance of computational role -- What do we now know about anti-CD20 and its importance? -- How do cancer cells become resistant to mAbs after receiving treatment? -- Resistance issue with anti-CD20 therapies and potential strategies for reversing their effect -- Computational techniques to design the therapeutic antibody -- Availability of antibody databases -- International Immunogenetics Information System (IMGT) -- Antibodypedia (an examination of antibodies against the human proteome from the perspective of the chromosome) -- TABS (Therapeutic Antibody Database) -- DrugBank -- Thera-SAbDab: The Therapeutic Structural Antibody Database -- Advantages and disadvantages of therapeutic antibodies -- Advantages -- Disadvantages -- Possible side effects -- Current limitations with production cost -- Future -- Predictive biomarkers-A therapeutic response against cancer -- Conclusions -- Acknowledgments -- References -- Chapter 2: Anti-CD20 antibody treatment for B-cell malignancies -- Introduction -- B-cell malignancies -- Diffuse large B-cell lymphoma (DLBCL) -- Follicular lymphoma (FL). , Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) -- Mantle cell lymphoma (MCL) -- Marginal zone lymphomas (MZLs) -- Burkitt lymphoma (BL) -- Lymphoplasmacytic lymphoma (LPL) -- Hairy cell leukemia (HCL) -- Primary large B-cell lymphoma of immune-privileged sites -- Plasma cell myeloma (PCM) -- Mechanism of B-cell carcinogenesis/lymphomagenesis -- BCR signaling and cell survival in B-cell malignancies -- Chromosomal translocations, a survival factor in B-cell malignancies -- Microbial antigens in B-cell malignancies -- DNA repair and B-cell malignancies -- Role of epigenetic mechanisms in B-cell malignancies -- Tumor microenvironment and aging facilitates the progression of carcinogenesis -- Anti-CD20 antibodies -- Mechanism of action of anti-CD20 antibodies -- Efficacy of anti-CD20 antibodies therapy for B-cell malignancies and clinical trials -- Rituximab -- Tositumomab -- Ofatumumab -- Veltuzumab -- Ublituximab -- Side effects and prerequisites related to anti-CD20 antibodies therapy in B-cell malignancies -- Biomarkers for responsive anti-CD20 antibody therapy and solutions for refractory cases -- Future perspectives -- Conclusions -- References -- Chapter 3: Anti-CD20 antibody treatment for diffuse large B cell lymphoma: Genetic alterations and signaling pathways -- Introduction -- Mechanisms of rituximab -- Complement-dependent cytotoxicity -- Antibody-dependent cellular cytotoxicity -- Induction of apoptosis -- Genetic alterations and molecular mechanisms -- Cell signaling -- The NF-κB pathway -- The MAPK pathway and the Ras/Raf/MEK/ERK pathway -- The PI3K/AKT/MTOR pathway -- The JAK-STAT pathway -- BCR signaling -- Fas/FasL apoptotic pathway -- MYC, BCL2, BCL6 -- MYC -- BCL2 -- BCL6 -- Mutations in epigenetically regulated genes -- EZH2 and MLL -- CREBBP and EP300 -- Other frequent gene mutations -- TP53 -- PIM1 -- FOXO1. , Abnormal structure and function of CD20 -- Other possible mechanisms of rituximab resistance -- Immune escape -- B2M gene -- PD-1 and PD-L1 -- Changes in the TME -- Conclusions -- References -- Chapter 4: Non-Hodgkin lymphoma treated with anti-CD20 antibody-based immunochemotherapy -- Introduction -- Clinical experience -- Rituximab -- Follicular lymphoma -- Diffuse large B-cell lymphoma -- Other lymphomas -- Obinutuzumab -- Follicular lymphoma -- Diffuse large B-cell lymphoma -- Other lymphomas -- Ofatumumab -- Anti-CD20xCD3 bispecific antibodies -- Mosunetuzumab -- Glofitamab -- Epcoritamab -- Odronextamab -- Safety of BsAbs -- Anti-CD20 resistance -- Resistance to CDC -- Resistance to ADCC -- Resistance to apoptosis -- Loss of CD20 antigen -- Tumor microenvironment -- New approaches of B-cell-directed therapy: Beyond rituximab -- Type II anti-CD20 antibodies -- CD20xCD3 bispecific antibodies -- Anti-CD20 CAR-Ts -- Conclusions and future perspectives -- References -- Chapter 5: Targeted therapies for follicular lymphoma -- Introduction -- Lenalidomide -- PI3K inhibitors -- BTK inhibitors -- BCL-2 inhibitor -- EZH2 inhibitor -- Antibody-drug conjugates -- Bispecific antibody -- Chimeric antigen receptor T-cell therapy -- Conclusions -- Future perspectives -- Acknowledgments -- References -- Chapter 6: Treatment of relapsed follicular lymphoma -- Background -- Overview of treatment at relapse: Objectives of treatment -- Treatment in challenging situations: POD24 -- Treatment in challenging situations: Histological transformation -- Consolidation of the response: Maintenance -- Consolidation of the response: Stem cell transplantation (SCT) and cellular therapy (CT) -- Conclusions and future perspective -- References -- Chapter 7: New monoclonal antibodies for the treatment of acute lymphoblastic leukemia -- Introduction. , Approved antibody-based therapies for B-ALL -- CD20 and rituximab -- CD19 and blinatumomab -- CD22 and inotuzumab ozogamicin -- Antibody technology and CAR-T cell therapies -- Mechanisms of resistance to licensed antibody therapies -- Antigen alterations as a mechanism of resistance -- Antigen-independent mechanisms of resistance -- The future of licensed antibody-based immunotherapies in ALL -- Investigational therapies -- Novel approaches to existing immunotherapeutic targets for B-ALL -- Novel immunotherapeutic targets in B-ALL -- Antibody approaches to T-ALL -- Conclusions -- Acknowledgment -- References -- Chapter 8: Clinical relevance and therapeutic implications of CD20 expression in Hodgkin's lymphoma -- Introduction -- Etiopathogenesis of classical Hodgkins lymphoma (cHL) and the role of the CD20 marker -- Epstein-Barr virus (EBV) infection and HL -- Classical Hodgkins lymphoma (cHL) -- Pathophysiology -- The role of the tumor microenvironment (TME) and its interactions -- Antibody-dependent cellular cytotoxicity (ADCC) -- Complement-dependent cytotoxicity (CDC) -- Induction of direct cell death -- Impact of the CD20+ expression on the evolution and prognosis of HL -- Standard approach for HL treatment -- Clinical efficacy of anti-CD20 therapy on HL -- Proposed mechanisms of action of anti-CD20 therapy -- CD20, uncertainties, and the rationale for using monoclonal antibodies -- Immunogenicity, safety, and resistance mechanism to anti-CD20 antibodies -- Future perspectives -- Conclusions -- Acknowledgment -- References -- Part II: Resistance and affinity determination of anti-CD20 antibodies -- Chapter 9: Therapeutic options for rituximab-resistant patients -- Introduction -- Mechanisms of rituximab resistance -- Therapeutic options after rituximab resistance. , High-dose chemotherapy (HDT) and radio-immunotherapy (RIT) followed by autologous stem cell transplant (ASCT) -- Type II anti-CD20 mAbs -- Tositumomab -- Obinutuzumab -- Solutions to enhance the ADCC effect of anti-CD20 antibodies -- Second-generation and third-generation anti-CD20 antibodies -- Strategies to enhance the antitumor functions of immune effector cells -- Novel targets for mAbs -- Bispecific antibodies -- Small molecules -- Chimeric antigen receptor T cells (CAR-T) -- Watchful waiting (WW) -- Combination strategies -- Conclusions and perspectives -- Acknowledgments -- References -- Chapter 10: Mechanisms of resistance to anti-CD20 antibodies in lymphoid malignancies -- Introduction -- Factors influencing anti-CD20 mAb activity/resistance -- Pharmacokinetics -- CD20 alterations -- CD20 shaving and internalization -- MS4A1 (CD20 gene) mutations, deletions, and aberrant expression of its splicing variants -- Involvement of transcription factors in MS4A1 gene expression -- Epigenetic dysregulation of CD20 -- Resistance to antibody-dependent cell-mediated cytotoxicity (ADCC) -- Effector cell type -- Fcγ receptor polymorphisms -- Antibody type -- Tumor microenvironment -- Complement-mediated resistance -- Resistance to apoptosis -- Future perspectives -- Conclusions -- Acknowledgment -- References -- Chapter 11: Kinetic exclusion assay using cellular membranes for affinity determination of anti-CD20 antibody -- Anti-CD20 antibodies and biology -- CD20 biology -- Approved antibodies and indications -- Rituximab -- Ofatumumab -- Obinutuzumab -- Type I and Type II antibodies -- Resistance to anti-CD20 antibodies -- Anti-CD20 antibodies and biology summary -- Binding characterization technologies -- Surface plasmon resonance -- Flow cytometry -- KinExA -- Comparison of binding characterization technologies. , Important controls for analytical validity in KinExA experiments.

Additional Edition: Print version: Cho, William Chi Shing Resistance to Anti-CD20 Antibodies and Approaches for Their Reversal San Diego : Elsevier Science & Technology,c2023 ISBN 9780443192005

Language: English