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Evaluation of enzyme inhibitors in drug discovery : a guide for medicinal chemists and pharmacologists / / by Robert A. Copeland
| Evaluation of enzyme inhibitors in drug discovery : a guide for medicinal chemists and pharmacologists / / by Robert A. Copeland |
| Autore | Copeland Robert Allen |
| Edizione | [2nd ed.] |
| Pubbl/distr/stampa | Hoboken, N.J., : Wiley, c2013 |
| Descrizione fisica | 1 online resource (572 p.) |
| Disciplina | 615/.19 |
| Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
| ISBN |
1-118-54039-5
1-299-24215-4 1-118-54040-9 1-118-54028-X |
| Formato | Materiale a stampa  |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto | Machine generated contents note: Foreword.Preface.Acknowledgments.1. Why Enzymes as Drug Targets?1.1 Enzymes Are Essentials for Life.1.2 Enzyme Structure and Catalysis.1.3 Permutations of Enzyme Structure During Catalysis.1.4 Other Reasons for Studying Enzymes.1.5 Summary.References.2. Enzyme Reaction Mechanisms.2.1 Initial Binding of Substrate.2.2 Noncovalent Forces in Reversible Ligand Binding to Enzymes.2.2.1 Electrostatic Forces.2.2.2 Hydrogen Bonds.2.2.3 Hydrophobic Forces.2.2.4 van der Waals Forces.2.3 Transformations of the Bond Substrate.2.3.1 Strategies for Transition State Stabilization.2.3.2 Enzyme Active Sites Are Most Complementary to the Transition State Structure.2.4 Steady State Analysis of Enzyme Kinetics.2.4.1 Factors Affecting the Steady State Kinetic Constants.2.5 Graphical Determination of kcat and KM2.6 Reactions Involving Multiple Substates.2.6.1 Bisubstrate Reaction Mechanisms.2.7 Summary.References.3. Reversible Modes of Inhibitor Interactions with Enzymes.3.1 Enzyme-Inhibitor Binding Equilibria.3.2 Competitive Inhibition.3.3 Noncompetitive Inhibition.3.3.1 Mutual Exclusively Studies.3.4 Uncompetitive Inhibition.3.5 Inhibition Modality in Bisubstrate Reactions.3.6 Value of Knowing Inhibitor Modality.3.6.1 Quantitative Comparisons of Inhibitor Affinity.3.6.2 Relating Ki to Binding Energy.3.6.3 Defining Target Selectivity by Ki Values.3.6.4 Potential Advantages and Disadvantages of Different Inhibition Modalities In Vivo.3.6.5 Knowing Inhibition Modality Is Important for Structure-Based Lead Organization.3.7 Summary.References.4. Assay Considerations for Compound Library Screening.4.1 Defining Inhibition Signal Robustness, and Hit Criteria.4.2 Measuring Initial Velocity.4.2.1 End-Point and Kinetic Readouts.4.2.2 Effects of Enzyme Concentration.4.3 Balanced Assay Conditions.4.3.1 Balancing Conditions for Multisubstrate Reactions.4.4 Order of Reagent Addition.4.5 Use of Natural Substrates and Enzymes.4.6 Coupled Enzyme Assays.4.7 Hit Validation and Progression.4.8 Summary.References.5. Lead Optimization and Structure-Activity Relationships for Reversible Inhibitors.5.1 Concentration-Response Plots and IC50 Determination.5.1.1 The Hill Coefficient.5.1.2 Graphing and Reporting Concentration-Response Data.5.2 Testing for Reversibility.5.3 Determining Reversible Inhibition Modality and Dissociation Constant.5.4 Comparing Relative Affinity.5.4.1 Compound Selectivity.5.5 Associating Cellular Effects with Target Enzyme Inhibition.5.5.1 Cellular Phenotype Should Be Consistent with Genetic Knockout or Knockdown of the Target Enzyme.5.5.2 Cellular Activity Should Require a Certain Affinity for the target Enzyme.5.5.3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells.5.5.4 Cellular Phenotype Should Be Reversed by Cell-Permeable Product or Downstream Metabolites of the Target Enzyme Activity.5.5.5 Mutation of the Target Enzyme Should Lead to Resistance or Hypersensitivity to Inhibitors.5.6 Summary.References.6. Slow Binding Inhibitors.6.1 Determining kobs: The Rate Constant for Onset of Inhibition.6.2 Mechanisms of Slow Binding Inhibition.6.3 Determination of Mechanism and Assessment of True Affinity.6.3.1 Potential Clinical Advantages of Slow Off-rate Inhibitors.6.4 Determining Inhibition Modality for Slow Binding Inhibitors.6.5 SAR for Slow Binding Inhibitors.6.6 Some Examples of Pharmacologically Interesting Slow Binding Inhibitors.6.6.1 Examples of Scheme B: Inhibitors of Zinc Peptidases and Proteases.6.6.2 Example of Scheme C: Inhibition of Dihydrofolate Reductase by Methotresate.6.6.3 Example of Scheme C: Inhibition of Calcineurin by FKBP-Inhibitor Complexes.6.6.4 Example of Scheme C When Ki* << Ki: Aspartyl Protease Inhibitors.6.6.5 Example of Scheme C When k6 Is Very Small: Selective COX2 Inhibitors.6.7 Summary.References.7. Tight Binding Inhibitors.7.1 Effects of Tight Binding Inhibition Concentration-Response Data.7.2 The IC50 Value Depends on Kiapp and [E]T.7.3 Morrison's Quadratic Equation for Fiting Concentration-Response Data for Tight Binding Inhibitors.7.3.1 Optimizing Conditions for Kiapp Determination Using Morrison's Equation.7.3.2 Limits on Kiapp Determinations.7.3.3 Use of a Cubic Equation When Both Substrate and Inhibitor Are Tight Binding.7.4 Determining Modality for Tight Binding Enzyme Inhibitors.7.5 Tight Binding Inhibitors Often Display Slow Binding Behavior.7.6 Practical Approaches to Overcoming the Tight Binding Limit in Determine Ki.7.7 Enzyme-Reaction Intermediate Analogues as Example of Tight Binding Inhibitors.7.7.1 Bisubstrate Analogues.7.7.2 Testing for Transition State Mimicry.7.8 Potential Clinical Advantages of Tight Binding Inhibitors.7.9 Determination of [E]T Using Tight Binding Inhibitors.7.10 Summary.References.8. Irreversible Enzyme Inactivators.8.1 Kinetic Evaluation of Irreversible Enzyme Inactivators.8.2 Affinity Labels.8.2.1 Quiescent Affinity Labels.8.2.2 Potential Liabilities of Affinity Labels as Drugs.8.3 Mechanism-Based Inactivators.8.3.1 Distinguishing Features of Mechanism-Based Inactivation.8.3.2 Determination of the Partition Ratio.8.3.3 Potential Clinical Advantages of Mechanism-Based Inactivators.8.3.4 Examples of Mechanism-Based Inactivators as Drugs.8.4 Use of Affinity Labels as Mechanistic Tools.8.5 Summary.References.Appendix 1. Kinetic of Biochemical Reactions.A1.1 The Law of Mass Action and Reaction Order.A1.2 First-Order Reaction Kinetics.A1.3 Second-Order Reaction Kinetics.A1.4 Pseudo-First-Order Reaction Conditions.A1.5 Approach to Equilibrium: An Example of the Kinetics of Reversible Reactions.References.Appendix 2. Derivation of the Enzyme-Ligand Binding Isotherm Equation.References.Appendix 3. Serial Dilution Schemes.Index. |
| Record Nr. | UNINA-9910808406303321 |
Copeland Robert Allen
|
||
| Hoboken, N.J., : Wiley, c2013 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland
| Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland |
| Autore | Copeland Robert Allen |
| Pubbl/distr/stampa | Hoboken, N.J., : Wiley-Interscience, 2005 |
| Descrizione fisica | xvii, 271 p. : ill |
| Disciplina | 615/.19 |
| Collana | Methods of biochemical analysis |
| Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
| Soggetto genere / forma | Electronic books. |
| ISBN |
0-471-72327-4
1-280-25506-4 9786610255061 0-471-72326-6 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Record Nr. | UNINA-9910449948503321 |
|
Copeland Robert Allen
|
||
| Hoboken, N.J., : Wiley-Interscience, 2005 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland
| Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland |
| Autore | Copeland Robert Allen |
| Pubbl/distr/stampa | Hoboken, N.J., : Wiley-Interscience, 2005 |
| Descrizione fisica | xvii, 271 p. : ill |
| Disciplina | 615/.19 |
| Collana | Methods of biochemical analysis |
| Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
| ISBN |
0-471-72327-4
1-280-25506-4 9786610255061 0-471-72326-6 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Record Nr. | UNINA-9910783520003321 |
|
Copeland Robert Allen
|
||
| Hoboken, N.J., : Wiley-Interscience, 2005 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland
| Evaluation of enzyme inhibitors in drug discovery [[electronic resource] ] : a guide for medicinal chemists and pharmacologists / / Robert A. Copeland |
| Autore | Copeland Robert Allen |
| Edizione | [1st ed.] |
| Pubbl/distr/stampa | Hoboken, N.J., : Wiley-Interscience, 2005 |
| Descrizione fisica | xvii, 271 p. : ill |
| Disciplina | 615/.19 |
| Collana | Methods of biochemical analysis |
| Soggetto topico |
Enzyme inhibitors - Therapeutic use - Testing
Drugs - Design Enzyme inhibitors - Structure-activity relationships |
| ISBN |
0-471-72327-4
1-280-25506-4 9786610255061 0-471-72326-6 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Intro -- Evaluation of Enzyme Inhibitors in Drug Discovery -- Contents -- Foreword -- Preface -- Acknowledgments -- 1. Why Enzymes as Drug Targets? -- 1.1 Enzymes Are Essential for Life -- 1.2 Enzyme Structure and Catalysis -- 1.3 Permutations of Enzyme Structure during Catalysis -- 1.4 Other Reasons for Studying Enzymes -- 1.5 Summary -- References -- 2. Enzyme Reaction Mechanisms -- 2.1 Initial Binding of Substrate -- 2.2 Noncovalent Forces in Reversible Ligand Binding to Enzymes -- 2.2.1 Electrostatic Forces -- 2.2.2 Hydrogen Bonds -- 2.2.3 Hydrophobic Forces -- 2.2.4 van der Waals Forces -- 2.3 Transformations of the Bound Substrate -- 2.3.1 Strategies for Transition State Stabilization -- 2.3.2 Enzyme Active Sites Are Most Complementary to the Transition State Structure -- 2.4 Steady State Analysis of Enzyme Kinetics -- 2.4.1 Factors Affecting the Steady State Kinetic Constants -- 2.5 Graphical Determination of k(cat) and K(M) -- 2.6 Reactions Involving Multiple Substrates -- 2.6.1 Bisubstrate Reaction Mechanisms -- 2.7 Summary -- References -- 3. Reversible Modes of Inhibitor Interactions with Enzymes -- 3.1 Enzyme-Inhibitor Binding Equilibria -- 3.2 Competitive Inhibition -- 3.3 Noncompetititive Inhibition -- 3.3.1 Mutual Exclusivity Studies -- 3.4 Uncompetitive Inhibition -- 3.5 Inhibition Modality in Bisubstrate Reactions -- 3.6 Value of Knowing Inhibitor Modality -- 3.6.1 Quantitative Comparisons of Inhibitor Affinity -- 3.6.2 Relating K(i) to Binding Energy -- 3.6.3 Defining Target Selectivity by K(i) Values -- 3.6.4 Potential Advantages and Disadvantages of Different Inhibition Modalities In Vivo -- 3.6.5 Knowing Inhibition Modality Is Important for Structure-Based Lead Optimization -- 3.7 Summary -- References -- 4. Assay Considerations for Compound Library Screening -- 4.1 Defining Inhibition, Signal Robustness, and Hit Criteria.
4.2 Measuring Initial Velocity -- 4.2.1 End-Point and Kinetic Readouts -- 4.2.2 Effects of Enzyme Concentration -- 4.2.3 Other Factors Affecting Initial Velocity -- 4.3 Balanced Assay Conditions -- 4.3.1 Balancing Conditions for Multisubstrate Reactions -- 4.4 Order of Reagent Addition -- 4.5 Use of Natural Substrates and Enzymes -- 4.6 Coupled Enzyme Assays -- 4.7 Hit Validation and Progression -- 4.8 Summary -- References -- 5. Lead Optimization and Structure-Activity Relationships for Reversible Inhibitors -- 5.1 Concentration-Response Plots and IC(50) Determination -- 5.1.1 The Hill Coefficient -- 5.1.2 Graphing and Reporting Concentration-Response Data -- 5.2 Testing for Reversibility -- 5.3 Determining Reversible Inhibition Modality and Dissociation Constant -- 5.4 Comparing Relative Affinity -- 5.4.1 Compound Selectivity -- 5.5 Associating Cellular Effects with Target Enzyme Inhibition -- 5.5.1 Cellular Phenotype Should Be Consistent with Genetic Knockout or Knockdown of the Target Enzyme -- 5.5.2 Cellular Activity Should Require a Certain Affinity for the Target Enzyme -- 5.5.3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells -- 5.5.4 Cellular Phenotype Should Be Reversed by Cell-Permeable Product or Downstream Metabolites of the Target Enzyme Activity -- 5.5.5 Mutation of the Target Enzyme Should Lead to Resistance or Hypersensitivity to Inhibitors -- 5.6 Summary -- References -- 6. Slow Binding Inhibitors -- 6.1 Determining k(obs): The Rate Constant for Onset of Inhibition -- 6.2 Mechanisms of Slow Binding Inhibition -- 6.3 Determination of Mechanism and Assessment of True Affinity -- 6.3.1 Potential Clinical Advantages of Slow Off-rate Inhibitors -- 6.4 Determining Inhibition Modality for Slow Binding Inhibitors -- 6.5 SAR for Slow Binding Inhibitors. 6.6 Some Examples of Pharmacologically Interesting Slow Binding Inhibitors -- 6.6.1 Examples of Scheme B: Inhibitors of Zinc Peptidases and Proteases -- 6.6.2 Example of Scheme C: Inhibition of Dihydrofolate Reductase by Methotrexate -- 6.6.3 Example of Scheme C: Inhibition of Calcineurin by FKBP-Inhibitor Complexes -- 6.6.4 Example of Scheme C When K*(i) < -- < -- K(i): Aspartyl Protease Inhibitors -- 6.6.5 Example of Scheme C When k(6) Is Very Small: Selective COX2 Inhibitors -- 6.7 Summary -- References -- 7. Tight Binding Inhibitors -- 7.1 Effects of Tight Binding Inhibition Concentration-Response Data -- 7.2 The IC(50) Value Depends on K(app)(i) and [E](T) -- 7.3 Morrison's Quadratic Equation for Fitting Concentration-Response Data for Tight Binding Inhibitors -- 7.3.1 Optimizing Conditions for K(app)(i) Determination Using Morrison's Equation -- 7.3.2 Limits on K(app)(i) Determinations -- 7.3.3 Use of a Cubic Equation When Both Substrate and Inhibitor Are Tight Binding -- 7.4 Determining Modality for Tight Binding Enzyme Inhibitors -- 7.5 Tight Binding Inhibitors Often Display Slow Binding Behavior -- 7.6 Practical Approaches to Overcoming the Tight Binding Limit in Determining K(i) -- 7.7 Enzyme-Reaction Intermediate Analogues as Examples of Tight Binding Inhibitors -- 7.7.1 Bisubstrate Analogues -- 7.7.2 Testing for Transition State Mimicry -- 7.8 Potential Clinical Advantages of Tight Binding Inhibitors -- 7.9 Determination of [E](T) Using Tight Binding Inhibitors -- 7.10 Summary -- References -- 8. Irreversible Enzyme Inactivators -- 8.1 Kinetic Evaluation of Irreversible Enzyme Inactivators -- 8.2 Affinity Labels -- 8.2.1 Quiescent Affinity Labels -- 8.2.2 Potential Liabilities of Affinity Labels as Drugs -- 8.3 Mechanism-Based Inactivators -- 8.3.1 Distinguishing Features of Mechanism-Based Inactivation. 8.3.2 Determination of the Partition Ratio -- 8.3.3 Potential Clinical Advantages of Mechanism-Based Inactivators -- 8.3.4 Examples of Mechanism-Based Inactivators as Drugs -- 8.4 Use of Affinity Labels as Mechanistic Tools -- 8.5 Summary -- References -- Appendix 1. Kinetics of Biochemical Reactions -- A1.1 The Law of Mass Action and Reaction Order -- A1.2 First-Order Reaction Kinetics -- A1.3 Second-Order Reaction Kinetics -- A1.4 Pseudo-First-Order Reaction Conditions -- A1.5 Approach to Equilibrium: An Example of the Kinetics of Reversible Reactions -- References -- Appendix 2. Derivation of the Enzyme-Ligand Binding Isotherm Equation -- References -- Appendix 3. Serial Dilution Schemes -- Index. |
| Record Nr. | UNINA-9910827528903321 |
|
Copeland Robert Allen
|
||
| Hoboken, N.J., : Wiley-Interscience, 2005 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Flow cytometry in drug discovery and development [[electronic resource] /] / edited by Virginia M. Litwin, Philip Marder
| Flow cytometry in drug discovery and development [[electronic resource] /] / edited by Virginia M. Litwin, Philip Marder |
| Pubbl/distr/stampa | Hoboken, N.J., : Wiley, c2011 |
| Descrizione fisica | 1 online resource (370 p.) |
| Disciplina |
615.19
615/.19 |
| Altri autori (Persone) |
LitwinVirginia
MarderPhilip |
| Soggetto topico |
Flow cytometry
Drugs - Design |
| ISBN |
0-470-92278-8
1-283-91610-X 0-470-91008-9 0-470-91007-0 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto | pt. 1. Introduction / Philip Marder and Virginia Litwin -- pt. 2. Flow cytometry in the drug development process / Virginia Litwin and Philip Marder -- pt. 3. Validation and regulatory compliance / Virginia Litwin and Philip Marder -- pt. 4. Future directions / Virginia Litwin and Philip Marder. |
| Record Nr. | UNINA-9910140901703321 |
| Hoboken, N.J., : Wiley, c2011 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Flow cytometry in drug discovery and development [[electronic resource] /] / edited by Virginia M. Litwin, Philip Marder
| Flow cytometry in drug discovery and development [[electronic resource] /] / edited by Virginia M. Litwin, Philip Marder |
| Pubbl/distr/stampa | Hoboken, N.J., : Wiley, c2011 |
| Descrizione fisica | 1 online resource (370 p.) |
| Disciplina |
615.19
615/.19 |
| Altri autori (Persone) |
LitwinVirginia
MarderPhilip |
| Soggetto topico |
Flow cytometry
Drugs - Design |
| ISBN |
0-470-92278-8
1-283-91610-X 0-470-91008-9 0-470-91007-0 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto | pt. 1. Introduction / Philip Marder and Virginia Litwin -- pt. 2. Flow cytometry in the drug development process / Virginia Litwin and Philip Marder -- pt. 3. Validation and regulatory compliance / Virginia Litwin and Philip Marder -- pt. 4. Future directions / Virginia Litwin and Philip Marder. |
| Record Nr. | UNINA-9910831051303321 |
| Hoboken, N.J., : Wiley, c2011 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Fragment-based drug discovery : lessons and outlook / / edited by Daniel A. Erlanson and Wolfgang Jahnke
| Fragment-based drug discovery : lessons and outlook / / edited by Daniel A. Erlanson and Wolfgang Jahnke |
| Pubbl/distr/stampa | Wiesbaden, Germany : , : Wiley-VCH Verlag GmbH & Co. KGaA, , 2016 |
| Descrizione fisica | 1 online resource (527 p.) |
| Disciplina | 615.19 |
| Collana | Methods and Principles in Medicinal Chemistry |
| Soggetto topico |
Drug development
Drugs - Design Ligands (Biochemistry) Drug Discovery LIgands |
| ISBN |
3-527-68362-3
3-527-68360-7 3-527-68361-5 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Fragment-based Drug Discovery: Lessons and Outlook; Contents; Contributors; Preface; A Personal Foreword; Part I: The Concept of Fragment-based Drug Discovery; 1. The Role of Fragment-based Discovery in Lead Finding; 1.1 Introduction; 1.2 What is FBLD?; 1.3 FBLD: Current Practice; 1.3.1 Using Fragments: Conventional Targets; 1.3.2 Using Fragments: Unconventional Targets; 1.4 What do Fragments Bring to Lead Discovery?; 1.5 How did We Get Here?; 1.5.1 Evolution of the Early Ideas and History; 1.5.2 What has Changed Since the First Book was Published in 2006?
1.6 Evolution of the Methods and Their Application Since 20051.6.1 Developments in Fragment Libraries; 1.6.2 Fragment Hit Rate and Druggability; 1.6.3 Developments in Fragment Screening; 1.6.4 Ways of Evolving Fragments; 1.6.5 Integrating Fragments Alongside Other Lead-Finding Strategies; 1.6.6 Fragments Can be Selective; 1.6.7 Fragment Binding Modes; 1.6.8 Fragments, Chemical Space, and Novelty; 1.7 Current Application and Impact; 1.8 Future Opportunities; References; 2. Selecting the Right Targets for Fragment-Based Drug Discovery; 2.1 Introduction 2.2 Properties of Targets and Binding Sites2.3 Assessing Druggability; 2.4 Properties of Ligands and Drugs; 2.5 Case Studies; 2.5.1 Case Study 1: Inhibitors of Apoptosis Proteins (IAPs); 2.5.2 Case Study 2: HCV-NS3; 2.5.3 Case Study 3: PKM2; 2.5.4 Case Study 4: Soluble Adenylate Cyclase; 2.6 Conclusions; References; 3. Enumeration of Chemical Fragment Space; 3.1 Introduction; 3.2 The Enumeration of Chemical Space; 3.2.1 Counting and Sampling Approaches; 3.2.2 Enumeration of the Chemical Universe Database GDB; 3.2.3 GDB Contents; 3.3 Using and Understanding GDB; 3.3.1 Drug Discovery 3.3.2 The MQN System3.3.3 Other Fingerprints; 3.4 Fragments from GDB; 3.4.1 Fragment Replacement; 3.4.2 Shape Diversity of GDB Fragments; 3.4.3 Aromatic Fragments from GDB; 3.5 Conclusions and Outlook; Acknowledgment; References; 4. Ligand Efficiency Metrics and their Use in Fragment Optimizations; 4.1 Introduction; 4.2 Ligand Efficiency; 4.3 Binding Thermodynamics and Efficiency Indices; 4.4 Enthalpic Efficiency Indices; 4.5 Lipophilic Efficiency Indices; 4.6 Application of Efficiency Indices in Fragment-Based Drug Discovery Programs; 4.7 Conclusions; References Part II: Methods and Approaches for Fragment-based Drug Discovery5. Strategies for Fragment Library Design; 5.1 Introduction; 5.2 Aims; 5.3 Progress; 5.3.1 BDDP Fragment Library Design: Maximizing Diversity; 5.3.2 Assessing Three-Dimensionality; 5.3.3 3DFrag Consortium; 5.3.4 Commercial Fragment Space Analysis; 5.3.5 BDDP Fragment Library Design; 5.3.6 Fragment Complexity; 5.3.6.1 Diversity-Oriented Synthesis-Derived Fragment-Like Molecules; 5.4 Future Plans; 5.5 Summary; 5.6 Key Achievements; References 6. The Synthesis of Biophysical Methods In Support of Robust Fragment-Based Lead Discovery |
| Record Nr. | UNINA-9910137167803321 |
| Wiesbaden, Germany : , : Wiley-VCH Verlag GmbH & Co. KGaA, , 2016 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Fragment-based drug discovery : lessons and outlook / / edited by Daniel A. Erlanson and Wolfgang Jahnke
| Fragment-based drug discovery : lessons and outlook / / edited by Daniel A. Erlanson and Wolfgang Jahnke |
| Pubbl/distr/stampa | Wiesbaden, Germany : , : Wiley-VCH Verlag GmbH & Co. KGaA, , 2016 |
| Descrizione fisica | 1 online resource (527 p.) |
| Disciplina | 615.19 |
| Collana | Methods and Principles in Medicinal Chemistry |
| Soggetto topico |
Drug development
Drugs - Design Ligands (Biochemistry) Drug Discovery LIgands |
| ISBN |
3-527-68362-3
3-527-68360-7 3-527-68361-5 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Fragment-based Drug Discovery: Lessons and Outlook; Contents; Contributors; Preface; A Personal Foreword; Part I: The Concept of Fragment-based Drug Discovery; 1. The Role of Fragment-based Discovery in Lead Finding; 1.1 Introduction; 1.2 What is FBLD?; 1.3 FBLD: Current Practice; 1.3.1 Using Fragments: Conventional Targets; 1.3.2 Using Fragments: Unconventional Targets; 1.4 What do Fragments Bring to Lead Discovery?; 1.5 How did We Get Here?; 1.5.1 Evolution of the Early Ideas and History; 1.5.2 What has Changed Since the First Book was Published in 2006?
1.6 Evolution of the Methods and Their Application Since 20051.6.1 Developments in Fragment Libraries; 1.6.2 Fragment Hit Rate and Druggability; 1.6.3 Developments in Fragment Screening; 1.6.4 Ways of Evolving Fragments; 1.6.5 Integrating Fragments Alongside Other Lead-Finding Strategies; 1.6.6 Fragments Can be Selective; 1.6.7 Fragment Binding Modes; 1.6.8 Fragments, Chemical Space, and Novelty; 1.7 Current Application and Impact; 1.8 Future Opportunities; References; 2. Selecting the Right Targets for Fragment-Based Drug Discovery; 2.1 Introduction 2.2 Properties of Targets and Binding Sites2.3 Assessing Druggability; 2.4 Properties of Ligands and Drugs; 2.5 Case Studies; 2.5.1 Case Study 1: Inhibitors of Apoptosis Proteins (IAPs); 2.5.2 Case Study 2: HCV-NS3; 2.5.3 Case Study 3: PKM2; 2.5.4 Case Study 4: Soluble Adenylate Cyclase; 2.6 Conclusions; References; 3. Enumeration of Chemical Fragment Space; 3.1 Introduction; 3.2 The Enumeration of Chemical Space; 3.2.1 Counting and Sampling Approaches; 3.2.2 Enumeration of the Chemical Universe Database GDB; 3.2.3 GDB Contents; 3.3 Using and Understanding GDB; 3.3.1 Drug Discovery 3.3.2 The MQN System3.3.3 Other Fingerprints; 3.4 Fragments from GDB; 3.4.1 Fragment Replacement; 3.4.2 Shape Diversity of GDB Fragments; 3.4.3 Aromatic Fragments from GDB; 3.5 Conclusions and Outlook; Acknowledgment; References; 4. Ligand Efficiency Metrics and their Use in Fragment Optimizations; 4.1 Introduction; 4.2 Ligand Efficiency; 4.3 Binding Thermodynamics and Efficiency Indices; 4.4 Enthalpic Efficiency Indices; 4.5 Lipophilic Efficiency Indices; 4.6 Application of Efficiency Indices in Fragment-Based Drug Discovery Programs; 4.7 Conclusions; References Part II: Methods and Approaches for Fragment-based Drug Discovery5. Strategies for Fragment Library Design; 5.1 Introduction; 5.2 Aims; 5.3 Progress; 5.3.1 BDDP Fragment Library Design: Maximizing Diversity; 5.3.2 Assessing Three-Dimensionality; 5.3.3 3DFrag Consortium; 5.3.4 Commercial Fragment Space Analysis; 5.3.5 BDDP Fragment Library Design; 5.3.6 Fragment Complexity; 5.3.6.1 Diversity-Oriented Synthesis-Derived Fragment-Like Molecules; 5.4 Future Plans; 5.5 Summary; 5.6 Key Achievements; References 6. The Synthesis of Biophysical Methods In Support of Robust Fragment-Based Lead Discovery |
| Record Nr. | UNINA-9910676628503321 |
| Wiesbaden, Germany : , : Wiley-VCH Verlag GmbH & Co. KGaA, , 2016 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Fragment-based drug discovery [[electronic resource] ] : a practical approach / / editors, Edward R. Zartler, Michael J. Shapiro
| Fragment-based drug discovery [[electronic resource] ] : a practical approach / / editors, Edward R. Zartler, Michael J. Shapiro |
| Pubbl/distr/stampa | Chichester, U.K., : John Wiley & Sons, 2008 |
| Descrizione fisica | 1 online resource (297 p.) |
| Disciplina |
615.19
615/.19 |
| Altri autori (Persone) |
ZartlerEdward
ShapiroMichael (Michael J.) |
| Soggetto topico |
Drug development
Drugs - Design Ligands (Biochemistry) |
| Soggetto genere / forma | Electronic books. |
| ISBN |
1-282-34275-4
9786612342752 0-470-72155-3 0-470-72156-1 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Fragment-Based Drug Discovery; Contents; List of Contributors; 1 Introduction to Fragment-based Drug Discovery; 2 Designing a Fragment Process to Fit Your Needs; 3 Assembling a Fragment Library; 4 Practical Aspects of Using NMR in Fragment-based Screening; 5 Application of Protein-Ligand NOE Matching to the Rapid Evaluation of Fragment Binding Poses; 6 Target-immobilized NMR Screening: Validation and Extension to Membrane Proteins; 7 In Situ Fragment-based Medicinal Chemistry: Screening by Mass Spectrometry; 8 Computational Approaches to Fragment and Substructure Discovery and Evaluation
9 Virtual Fragment Scanning: Current Trends, Applications and Web-based Tools10 Capture Methods for Fragment-based Discovery; 11 Identification of High-affinity -Secretase Inhibitors Using Fragment-based Lead Generation; Index |
| Record Nr. | UNINA-9910144402103321 |
| Chichester, U.K., : John Wiley & Sons, 2008 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Fragment-based drug discovery [[electronic resource] ] : a practical approach / / editors, Edward R. Zartler, Michael J. Shapiro
| Fragment-based drug discovery [[electronic resource] ] : a practical approach / / editors, Edward R. Zartler, Michael J. Shapiro |
| Pubbl/distr/stampa | Chichester, U.K., : John Wiley & Sons, 2008 |
| Descrizione fisica | 1 online resource (297 p.) |
| Disciplina |
615.19
615/.19 |
| Altri autori (Persone) |
ZartlerEdward
ShapiroMichael (Michael J.) |
| Soggetto topico |
Drug development
Drugs - Design Ligands (Biochemistry) |
| ISBN |
1-282-34275-4
9786612342752 0-470-72155-3 0-470-72156-1 |
| Formato | Materiale a stampa |
| Livello bibliografico | Monografia |
| Lingua di pubblicazione | eng |
| Nota di contenuto |
Fragment-Based Drug Discovery; Contents; List of Contributors; 1 Introduction to Fragment-based Drug Discovery; 2 Designing a Fragment Process to Fit Your Needs; 3 Assembling a Fragment Library; 4 Practical Aspects of Using NMR in Fragment-based Screening; 5 Application of Protein-Ligand NOE Matching to the Rapid Evaluation of Fragment Binding Poses; 6 Target-immobilized NMR Screening: Validation and Extension to Membrane Proteins; 7 In Situ Fragment-based Medicinal Chemistry: Screening by Mass Spectrometry; 8 Computational Approaches to Fragment and Substructure Discovery and Evaluation
9 Virtual Fragment Scanning: Current Trends, Applications and Web-based Tools10 Capture Methods for Fragment-based Discovery; 11 Identification of High-affinity -Secretase Inhibitors Using Fragment-based Lead Generation; Index |
| Record Nr. | UNINA-9910830794403321 |
| Chichester, U.K., : John Wiley & Sons, 2008 | ||
| Materiale a stampa | ||
| Lo trovi qui: Univ. Federico II | ||
| ||
Soggetto topico
-
Drugs - Design
(283)
- Pharmaceutical chemistry (86)
- Drug development (61)
- Drug Design (35)
- Drug delivery systems (16)