DRUG DISCOVERY
Drug Discovery without a lead
LEAD DISCOVERY/IDENTIFICATION
LEAD MODIFICATION
CONCEPT OF PRODRUGS AND SOFT DRUGS
DRUG RECEPTOR INTERACTIONS
THE DRUG DESIGN AND DEVELOPMENT BASED ON DRUG DISCOVERY ,HERE ITS NEED RATIONALE ARE EXPLAINED ALSO QSAR, MOLECULAR DOCKING ITS HISTORY NEED, STRUCTURE BASED DRUG DESIGN IN EASY WAY WE HAVE MENTIONED. THIS WILL MAKE READERS EASY TO COLLECT DATA AT A PLACE ALL OVER THIS IS FOR PHARMA STUDENTS, ACADEMICS, PROFESSIONL AND OST USEFUL FOR RESEARCHERS.
THANK YOU
HOPE YOU WILL LIKE AND SHARE
Relationship between hansch analysis and free wilson analysisKomalJAIN122
This document provides an overview of quantitative structure-activity relationship (QSAR) modeling techniques including Hansch analysis, Free-Wilson analysis, and Topliss schemes. It discusses how QSAR relates the biological activity of drugs to their physicochemical properties through equations. Specifically, it explains that Hansch equations relate activity to hydrophobicity, electronic effects, and steric factors. Examples of Hansch equations are provided. The Free-Wilson approach derives equations based on the presence or absence of substituents. Topliss schemes provide a methodical approach to substituent selection for optimization.
This document discusses structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR). SAR involves analyzing how changes to a molecule's structure affect its biological activity. QSAR establishes a mathematical relationship between biological activity and a molecule's geometric and chemical characteristics. SAR identifies important functional groups for binding through systematic structural modifications. QSAR analysis can be 2D, considering factors like those in Hansch analysis or Free-Wilson analysis, or 3D, considering steric and electrostatic values as well as hydrogen bonding abilities as in Comparative Molecular Field Analysis or Comparative Molecular Similarity Index Analysis.
The document discusses lead identification in drug development. It defines a lead compound as one that shows desired pharmaceutical activity and could potentially be developed into a drug. The document outlines the content to be presented, including an introduction to lead identification, what a lead is, properties of leads, and methods for identifying leads. Key methods discussed are random screening, non-random screening, high-throughput screening, and structure-based drug design.
This document discusses structure-based drug design. It begins by explaining that structure-based drug design relies on knowledge of the three-dimensional structure of biological targets, usually determined through methods like X-ray crystallography. The structure of the target is then used to design ligands that will bind to the target. The process involves identifying drug targets, determining the target's structure, performing computer-aided drug design to identify potential binding ligands, and building or modifying ligands to optimize binding to the target.
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
SAR versus QSAR, History and development of QSAR, Types of physicochemical
parameters, experimental and theoretical approaches for the determination of
physicochemical parameters such as Partition coefficient, Hammet’s substituent
constant and Taft’s steric constant. Hansch analysis, Free Wilson analysis, 3D-QSAR
approaches like COMFA and COMSIA.
THE DRUG DESIGN AND DEVELOPMENT BASED ON DRUG DISCOVERY ,HERE ITS NEED RATIONALE ARE EXPLAINED ALSO QSAR, MOLECULAR DOCKING ITS HISTORY NEED, STRUCTURE BASED DRUG DESIGN IN EASY WAY WE HAVE MENTIONED. THIS WILL MAKE READERS EASY TO COLLECT DATA AT A PLACE ALL OVER THIS IS FOR PHARMA STUDENTS, ACADEMICS, PROFESSIONL AND OST USEFUL FOR RESEARCHERS.
THANK YOU
HOPE YOU WILL LIKE AND SHARE
Relationship between hansch analysis and free wilson analysisKomalJAIN122
This document provides an overview of quantitative structure-activity relationship (QSAR) modeling techniques including Hansch analysis, Free-Wilson analysis, and Topliss schemes. It discusses how QSAR relates the biological activity of drugs to their physicochemical properties through equations. Specifically, it explains that Hansch equations relate activity to hydrophobicity, electronic effects, and steric factors. Examples of Hansch equations are provided. The Free-Wilson approach derives equations based on the presence or absence of substituents. Topliss schemes provide a methodical approach to substituent selection for optimization.
This document discusses structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR). SAR involves analyzing how changes to a molecule's structure affect its biological activity. QSAR establishes a mathematical relationship between biological activity and a molecule's geometric and chemical characteristics. SAR identifies important functional groups for binding through systematic structural modifications. QSAR analysis can be 2D, considering factors like those in Hansch analysis or Free-Wilson analysis, or 3D, considering steric and electrostatic values as well as hydrogen bonding abilities as in Comparative Molecular Field Analysis or Comparative Molecular Similarity Index Analysis.
The document discusses lead identification in drug development. It defines a lead compound as one that shows desired pharmaceutical activity and could potentially be developed into a drug. The document outlines the content to be presented, including an introduction to lead identification, what a lead is, properties of leads, and methods for identifying leads. Key methods discussed are random screening, non-random screening, high-throughput screening, and structure-based drug design.
This document discusses structure-based drug design. It begins by explaining that structure-based drug design relies on knowledge of the three-dimensional structure of biological targets, usually determined through methods like X-ray crystallography. The structure of the target is then used to design ligands that will bind to the target. The process involves identifying drug targets, determining the target's structure, performing computer-aided drug design to identify potential binding ligands, and building or modifying ligands to optimize binding to the target.
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
SAR versus QSAR, History and development of QSAR, Types of physicochemical
parameters, experimental and theoretical approaches for the determination of
physicochemical parameters such as Partition coefficient, Hammet’s substituent
constant and Taft’s steric constant. Hansch analysis, Free Wilson analysis, 3D-QSAR
approaches like COMFA and COMSIA.
This document discusses the key principles and processes involved in drug discovery and drug-receptor interactions. It outlines the steps of choosing a disease target, identifying a bioassay to test potential drug candidates, finding and isolating lead compounds, determining a drug's structure and effects, and identifying forces that cause drug-receptor binding such as covalent bonding, hydrogen bonding, and hydrophobic interactions. The goal is to discover and develop safe and effective therapeutic drugs through a scientific process.
Presentation on insilico drug design and virtual screeningJoon Jyoti Sahariah
This presentation discusses in silico drug design and virtual screening techniques. It defines in silico drug design as using computational software to perform drug design based on knowledge of a biological target. The presentation outlines two main types of in silico drug design: ligand-based, which uses known ligands to derive a pharmacophore when the receptor is unknown, and structure-based, which relies on knowledge of the 3D receptor structure. It also describes virtual screening techniques as automatically evaluating large compound libraries for likelihood of binding to a target protein using computer programs based on ligand or structure models.
PHARMACOHORE MAPPING AND VIRTUAL SCRRENING FOR RESEARCH DEPARTMENTShikha Popali
THE PHARMACOPHORE MAPPING AND VIRTUAL SCRRENING , THESE PRESENTATION INCLUDES THE DEATIL ACCOUNT ON PHARMACOPHORE, MAPPING, ITS IDENTIFIATION FEATURES, ITS CONFORMATIONAL SEARCH, INSILICO DRUG DESIGN, VIRTUAL SCREENING, PHARMACOPHORE BASED SCREENING
This presentation discusses drug target identification and validation. It introduces drug targets as specific sites where drugs bind to exert their therapeutic effects. Target identification methods include genomics, proteomics, and bioinformatics. Targets are then validated using techniques like siRNAs and antisense oligonucleotides to demonstrate the functional role of targets in disease and ensure drug interactions produce the desired therapeutic response.
The Free-Wilson approach correlates the biological activity of parent structures and analogues bearing different substituents. In 1964, Free and Wilson derived a mathematical model representing structural features as 1s and 0s correlated to biological activity. The method assumes substituents make additive contributions to biological activity. Free-Wilson analysis directly relates structural features to biological properties using only presence/absence of substituents as descriptors. It represents activity as the sum of group contributions and a reference compound activity. Drawbacks include needing substitution at two positions and only predicting combinations previously analyzed.
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
This document summarizes the main types of biological drug targets: receptors. It discusses four main classes of receptors: 1) G-protein coupled receptors, which bind ligands and activate G-proteins to interact with ion channels or enzymes, 2) ligand gated ion channel receptors, which open channels to allow ion passage upon ligand binding, 3) enzyme linked receptors with intracellular enzyme domains that are activated by ligand binding to induce intracellular signaling cascades, and 4) nuclear receptors within cells that directly bind DNA to regulate gene expression in response to ligands such as steroid hormones.
This document provides an overview of pharmacophore mapping and pharmacophore-based screening. It defines a pharmacophore as the pattern of molecular features responsible for a drug's biological activity. The key steps in pharmacophore modeling are identifying common binding elements in active compounds, generating potential ligand conformations, and determining the 3D relationships between pharmacophore elements. Pharmacophore models can be generated manually based on known active ligands or automatically using software. Receptor-based pharmacophore generation uses the 3D structure of the target protein to identify favorable binding sites. Overall, pharmacophore mapping is used in computer-aided drug design to identify novel ligands that interact with the same biological target.
This document provides an overview of prodrug design. It defines a prodrug as an inactive derivative of a drug molecule that undergoes biotransformation to release the active drug. Prodrugs are classified based on their structure and include carrier-linked, bipartite, tripartite, mutual, and bioprecursor prodrugs. The document discusses various rationales for prodrug design such as improving solubility, absorption, patient acceptability, and site-specific drug delivery. Common functional groups used in prodrugs include esters, amides, phosphates, and carbamates. The document also covers practical considerations and approaches for overcoming limitations like pre-systemic metabolism and blood-brain barrier penetration.
Molecular docking is a method for predicting how two molecules, such as a ligand and its protein target, will interact and fit together in three dimensions. Docking has become an important tool in drug discovery for identifying potential binding conformations between drug candidates and protein targets. The key steps in a typical docking workflow involve selecting the receptor and ligand molecules, then using software to computationally predict the orientation of binding and evaluate the fit through scoring functions. Popular molecular docking software packages include AutoDock, GOLD, and Glide. Applications of docking include virtual screening in drug discovery and lead optimization.
In this slide I covered the detailed about hansch analysis, Free-Wilson analysis, and Mixed approach. I also gave a detailed application for each points.
The document discusses pharmacophores, which are abstract descriptions of molecular features necessary for molecular recognition between a ligand and biological macromolecule. A pharmacophore consists of 3D structural features like hydrophobic groups and hydrogen bond donors/acceptors. Pharmacophore mapping is used to define pharmacophoric features and align molecules to identify common binding elements responsible for biological activity. Pharmacophore models can be used in virtual screening to filter large databases and identify new compounds that may bind similarly to known active molecules. The document provides details on different approaches for pharmacophore generation and searching compound libraries.
The document provides an overview of the modern drug discovery process, focusing on lead identification and lead optimization. It discusses how lead compounds are initially identified through screening compound libraries or structure-based drug design. These leads are then optimized through chemical modifications to improve properties like efficacy, potency, pharmacokinetics and toxicity profile. The goal is to develop compounds suitable for preclinical and clinical testing towards becoming an approved drug. Methods for lead optimization include modifying functional groups, exploring structure-activity relationships, and altering aspects like stereochemistry.
Pharmacophore modeling identifies key molecular features necessary for drug-target binding and biological response. It represents molecules schematically in 2D or 3D. Pharmacophore features include hydrogen bond donors/acceptors, aromaticity, hydrophobicity and hydrophilicity. Pharmacophore models are used for virtual screening to identify molecules that may activate or inhibit a target. There are two main types: ligand-based models extract common features of known ligands, while structure-based models define features from protein-ligand complex structures. Both aim to encode the optimal 3D arrangement of interactions between ligands and targets.
The document outlines the key stages of drug discovery:
1. Target identification involves finding the specific biomolecule target of a drug.
2. Target validation helps evaluate the potential of a target through assays and screening to find initial hits.
3. Lead discovery uses screening methods like molecular modeling or combinational chemistry to identify initial compounds ("leads") that interact with the target.
4. Lead optimization chemically modifies the leads to improve efficacy, safety and other drug properties.
5. Pre-clinical safety involves animal testing, toxicity studies and formulation before clinical trials in humans.
This document discusses various applications of quantitative structure-activity relationships (QSAR) in drug research and development. It describes how QSAR can provide information on receptor sites from enzyme inhibition studies, help understand the importance of physicochemical properties like log P values, and enable the use of bioisosterism to modify compounds. QSAR has correctly predicted drug activity and toxicity and is useful in drug design before compounds are synthesized.
LEAD IDENTIFICATION BY SUHAS PATIL (S.K.)suhaspatil114
This document provides an overview of lead identification in drug discovery. It discusses various methods for identifying lead compounds, including combinatorial chemistry, high-throughput screening, and in silico lead discovery techniques. Combinatorial chemistry allows for the rapid production and screening of large compound libraries. High-throughput screening assays test large numbers of compounds against biological targets using automated technologies. In silico methods like molecular docking use computer simulations to predict how compounds may bind and interact with targets. The goal is to find initial "hit" compounds that can then be optimized into drug candidates.
The document discusses quantitative structure-activity relationships (QSAR), which attempt to correlate biological activity to measurable molecular properties using mathematical equations. It notes that QSAR can be used to predict the activity of new compounds by deriving rules from a small set of experimentally tested compounds. Common molecular properties studied in QSAR include lipophilicity, electronic effects, and steric effects. Lipophilicity is often represented by log P values, while electronic and steric effects may be quantified using substituent constants like Hammett's σ and Taft's Es respectively. Different QSAR methods are outlined including linear free energy relationships and molecular modeling approaches.
In Silico methods for ADMET prediction of new moleculesMadhuraDatar
The document discusses the importance of predicting absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of new molecules in silico during drug design. It describes how ADMET prediction techniques have evolved since 1863 and helped advance drug development. Factors considered in developing ADMET prediction models include the model purpose, required prediction speed and accuracy. Common molecular descriptors used in these models are also discussed. The document outlines methods for predicting various ADMET properties like permeability, solubility, distribution and metabolism in silico. Recent tools for computational ADMET prediction are also mentioned.
This document provides an overview of prodrug design and practical considerations. It defines prodrugs as chemically inert precursors that release the active pharmacological compound. Prodrugs are classified based on their carrier and linker groups. The rationale for prodrug design includes improving solubility, enhancing membrane permeability, reducing pre-systemic metabolism, and targeting delivery to specific sites. Practical considerations for prodrug design involve the use of ester, amide, phosphate and carbamate groups to link the drug. The document discusses several examples of prodrugs and their advantages over parent drugs.
Drug discovery, Design & development basicsResearchsio
Drug discovery and development is a multi-step process that begins with identifying a disease target and ends with marketing an approved drug. Key steps include finding a lead compound through screening libraries or natural sources, optimizing the lead through structure-activity relationships to improve potency and safety, and conducting preclinical and clinical trials to prove a drug's efficacy and safety in humans. The overall goal is to take a biologically active lead and design analogs with improved target binding, pharmacokinetic properties, toxicity profile, and manufacturability.
This document discusses prodrug design. It defines prodrugs as pharmacologically inert derivatives that can be converted in vivo to the active drug molecule. The goals of prodrug design are to overcome undesirable drug properties related to absorption, distribution, metabolism and toxicity. Examples are given of prodrugs that increase oral absorption or provide targeted delivery to tumors. Prodrugs are evaluated based on their physicochemical properties and pharmacokinetic profile to ensure they are converted to the active drug molecule.
This document discusses the key principles and processes involved in drug discovery and drug-receptor interactions. It outlines the steps of choosing a disease target, identifying a bioassay to test potential drug candidates, finding and isolating lead compounds, determining a drug's structure and effects, and identifying forces that cause drug-receptor binding such as covalent bonding, hydrogen bonding, and hydrophobic interactions. The goal is to discover and develop safe and effective therapeutic drugs through a scientific process.
Presentation on insilico drug design and virtual screeningJoon Jyoti Sahariah
This presentation discusses in silico drug design and virtual screening techniques. It defines in silico drug design as using computational software to perform drug design based on knowledge of a biological target. The presentation outlines two main types of in silico drug design: ligand-based, which uses known ligands to derive a pharmacophore when the receptor is unknown, and structure-based, which relies on knowledge of the 3D receptor structure. It also describes virtual screening techniques as automatically evaluating large compound libraries for likelihood of binding to a target protein using computer programs based on ligand or structure models.
PHARMACOHORE MAPPING AND VIRTUAL SCRRENING FOR RESEARCH DEPARTMENTShikha Popali
THE PHARMACOPHORE MAPPING AND VIRTUAL SCRRENING , THESE PRESENTATION INCLUDES THE DEATIL ACCOUNT ON PHARMACOPHORE, MAPPING, ITS IDENTIFIATION FEATURES, ITS CONFORMATIONAL SEARCH, INSILICO DRUG DESIGN, VIRTUAL SCREENING, PHARMACOPHORE BASED SCREENING
This presentation discusses drug target identification and validation. It introduces drug targets as specific sites where drugs bind to exert their therapeutic effects. Target identification methods include genomics, proteomics, and bioinformatics. Targets are then validated using techniques like siRNAs and antisense oligonucleotides to demonstrate the functional role of targets in disease and ensure drug interactions produce the desired therapeutic response.
The Free-Wilson approach correlates the biological activity of parent structures and analogues bearing different substituents. In 1964, Free and Wilson derived a mathematical model representing structural features as 1s and 0s correlated to biological activity. The method assumes substituents make additive contributions to biological activity. Free-Wilson analysis directly relates structural features to biological properties using only presence/absence of substituents as descriptors. It represents activity as the sum of group contributions and a reference compound activity. Drawbacks include needing substitution at two positions and only predicting combinations previously analyzed.
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
This document summarizes the main types of biological drug targets: receptors. It discusses four main classes of receptors: 1) G-protein coupled receptors, which bind ligands and activate G-proteins to interact with ion channels or enzymes, 2) ligand gated ion channel receptors, which open channels to allow ion passage upon ligand binding, 3) enzyme linked receptors with intracellular enzyme domains that are activated by ligand binding to induce intracellular signaling cascades, and 4) nuclear receptors within cells that directly bind DNA to regulate gene expression in response to ligands such as steroid hormones.
This document provides an overview of pharmacophore mapping and pharmacophore-based screening. It defines a pharmacophore as the pattern of molecular features responsible for a drug's biological activity. The key steps in pharmacophore modeling are identifying common binding elements in active compounds, generating potential ligand conformations, and determining the 3D relationships between pharmacophore elements. Pharmacophore models can be generated manually based on known active ligands or automatically using software. Receptor-based pharmacophore generation uses the 3D structure of the target protein to identify favorable binding sites. Overall, pharmacophore mapping is used in computer-aided drug design to identify novel ligands that interact with the same biological target.
This document provides an overview of prodrug design. It defines a prodrug as an inactive derivative of a drug molecule that undergoes biotransformation to release the active drug. Prodrugs are classified based on their structure and include carrier-linked, bipartite, tripartite, mutual, and bioprecursor prodrugs. The document discusses various rationales for prodrug design such as improving solubility, absorption, patient acceptability, and site-specific drug delivery. Common functional groups used in prodrugs include esters, amides, phosphates, and carbamates. The document also covers practical considerations and approaches for overcoming limitations like pre-systemic metabolism and blood-brain barrier penetration.
Molecular docking is a method for predicting how two molecules, such as a ligand and its protein target, will interact and fit together in three dimensions. Docking has become an important tool in drug discovery for identifying potential binding conformations between drug candidates and protein targets. The key steps in a typical docking workflow involve selecting the receptor and ligand molecules, then using software to computationally predict the orientation of binding and evaluate the fit through scoring functions. Popular molecular docking software packages include AutoDock, GOLD, and Glide. Applications of docking include virtual screening in drug discovery and lead optimization.
In this slide I covered the detailed about hansch analysis, Free-Wilson analysis, and Mixed approach. I also gave a detailed application for each points.
The document discusses pharmacophores, which are abstract descriptions of molecular features necessary for molecular recognition between a ligand and biological macromolecule. A pharmacophore consists of 3D structural features like hydrophobic groups and hydrogen bond donors/acceptors. Pharmacophore mapping is used to define pharmacophoric features and align molecules to identify common binding elements responsible for biological activity. Pharmacophore models can be used in virtual screening to filter large databases and identify new compounds that may bind similarly to known active molecules. The document provides details on different approaches for pharmacophore generation and searching compound libraries.
The document provides an overview of the modern drug discovery process, focusing on lead identification and lead optimization. It discusses how lead compounds are initially identified through screening compound libraries or structure-based drug design. These leads are then optimized through chemical modifications to improve properties like efficacy, potency, pharmacokinetics and toxicity profile. The goal is to develop compounds suitable for preclinical and clinical testing towards becoming an approved drug. Methods for lead optimization include modifying functional groups, exploring structure-activity relationships, and altering aspects like stereochemistry.
Pharmacophore modeling identifies key molecular features necessary for drug-target binding and biological response. It represents molecules schematically in 2D or 3D. Pharmacophore features include hydrogen bond donors/acceptors, aromaticity, hydrophobicity and hydrophilicity. Pharmacophore models are used for virtual screening to identify molecules that may activate or inhibit a target. There are two main types: ligand-based models extract common features of known ligands, while structure-based models define features from protein-ligand complex structures. Both aim to encode the optimal 3D arrangement of interactions between ligands and targets.
The document outlines the key stages of drug discovery:
1. Target identification involves finding the specific biomolecule target of a drug.
2. Target validation helps evaluate the potential of a target through assays and screening to find initial hits.
3. Lead discovery uses screening methods like molecular modeling or combinational chemistry to identify initial compounds ("leads") that interact with the target.
4. Lead optimization chemically modifies the leads to improve efficacy, safety and other drug properties.
5. Pre-clinical safety involves animal testing, toxicity studies and formulation before clinical trials in humans.
This document discusses various applications of quantitative structure-activity relationships (QSAR) in drug research and development. It describes how QSAR can provide information on receptor sites from enzyme inhibition studies, help understand the importance of physicochemical properties like log P values, and enable the use of bioisosterism to modify compounds. QSAR has correctly predicted drug activity and toxicity and is useful in drug design before compounds are synthesized.
LEAD IDENTIFICATION BY SUHAS PATIL (S.K.)suhaspatil114
This document provides an overview of lead identification in drug discovery. It discusses various methods for identifying lead compounds, including combinatorial chemistry, high-throughput screening, and in silico lead discovery techniques. Combinatorial chemistry allows for the rapid production and screening of large compound libraries. High-throughput screening assays test large numbers of compounds against biological targets using automated technologies. In silico methods like molecular docking use computer simulations to predict how compounds may bind and interact with targets. The goal is to find initial "hit" compounds that can then be optimized into drug candidates.
The document discusses quantitative structure-activity relationships (QSAR), which attempt to correlate biological activity to measurable molecular properties using mathematical equations. It notes that QSAR can be used to predict the activity of new compounds by deriving rules from a small set of experimentally tested compounds. Common molecular properties studied in QSAR include lipophilicity, electronic effects, and steric effects. Lipophilicity is often represented by log P values, while electronic and steric effects may be quantified using substituent constants like Hammett's σ and Taft's Es respectively. Different QSAR methods are outlined including linear free energy relationships and molecular modeling approaches.
In Silico methods for ADMET prediction of new moleculesMadhuraDatar
The document discusses the importance of predicting absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of new molecules in silico during drug design. It describes how ADMET prediction techniques have evolved since 1863 and helped advance drug development. Factors considered in developing ADMET prediction models include the model purpose, required prediction speed and accuracy. Common molecular descriptors used in these models are also discussed. The document outlines methods for predicting various ADMET properties like permeability, solubility, distribution and metabolism in silico. Recent tools for computational ADMET prediction are also mentioned.
This document provides an overview of prodrug design and practical considerations. It defines prodrugs as chemically inert precursors that release the active pharmacological compound. Prodrugs are classified based on their carrier and linker groups. The rationale for prodrug design includes improving solubility, enhancing membrane permeability, reducing pre-systemic metabolism, and targeting delivery to specific sites. Practical considerations for prodrug design involve the use of ester, amide, phosphate and carbamate groups to link the drug. The document discusses several examples of prodrugs and their advantages over parent drugs.
Drug discovery, Design & development basicsResearchsio
Drug discovery and development is a multi-step process that begins with identifying a disease target and ends with marketing an approved drug. Key steps include finding a lead compound through screening libraries or natural sources, optimizing the lead through structure-activity relationships to improve potency and safety, and conducting preclinical and clinical trials to prove a drug's efficacy and safety in humans. The overall goal is to take a biologically active lead and design analogs with improved target binding, pharmacokinetic properties, toxicity profile, and manufacturability.
This document discusses prodrug design. It defines prodrugs as pharmacologically inert derivatives that can be converted in vivo to the active drug molecule. The goals of prodrug design are to overcome undesirable drug properties related to absorption, distribution, metabolism and toxicity. Examples are given of prodrugs that increase oral absorption or provide targeted delivery to tumors. Prodrugs are evaluated based on their physicochemical properties and pharmacokinetic profile to ensure they are converted to the active drug molecule.
This document provides information on prodrugs and biotransformation of drugs. It defines a prodrug as a chemically modified drug precursor that releases the active drug upon biotransformation. The objectives of prodrug design are to improve pharmaceutical and pharmacokinetic properties like absorption. Drugs undergo biotransformation through enzymatic reactions in the liver and other tissues to make them more water soluble for excretion. Phase I and II reactions introduce functional groups and conjugate drugs to endogenous substrates, respectively. First pass metabolism can decrease bioavailability by metabolizing drugs before they reach systemic circulation.
Introduction of Veterinary pharmacologyQaline Giigii
This document provides an introduction to veterinary pharmacology. It discusses how pharmacology can be defined as the study of substances that interact with living systems, and how veterinary pharmacology specifically focuses on preventing, diagnosing and treating disease in animals. The document then summarizes that veterinary pharmacology has two main subdivisions: pharmacokinetics, which is what the body does to a drug, and pharmacodynamics, which is what the drug does to the body. Several key pharmacokinetic and pharmacodynamic concepts are then defined, including absorption, distribution, metabolism, excretion, drug receptors, and drug effects.
Introduction of Veterinary pharmacology Somaliland Dr.Osman Abdulahi FarahQaline Giigii
This course was prepared by Dr.Osman Abdulahi Farah
Cismaan shiine Lecturer of Gollis University Faculty of Agriculture and Veterinary Medicine 2014
The main content of this course including introduction of Veterinary Pharmacology, division of pharmacology and list of terms of terminology about veterinay pharmacology
This document discusses techniques for in silico lead discovery in drug development. It describes identifying a target and bioassay, finding a lead compound, isolating and purifying the compound, determining its structure, studying structure-activity relationships, and identifying the pharmacophore. Methods for identifying lead compounds include random screening, non-random screening, high-throughput screening, and structure-based drug design. After preclinical studies, compounds undergo clinical trials in four phases before potential release as an approved drug.
Drug design is the process of creating new drugs by modifying existing compounds to maximize desired effects and minimize undesirable effects. Several approaches are used, including computational tools, structure-guided methods, and gene expression analysis software. Molecular modification involves chemically altering a known compound to enhance its usefulness as a drug. Some advantages include a higher likelihood of similar pharmacological properties to the original compound. Molecular dissociation and association are general processes used in molecular modification. Special processes include introducing or removing functional groups like double bonds or chiral centers. Antimetabolites are compounds that interfere with metabolism by mimicking normal metabolites. They are used as cancer treatments and antibiotics. Enzyme inhibitors are molecules that bind to enzymes and block their activity, either by binding to
The document discusses mutual prodrugs, which are composed of two pharmacologically active drug compounds that are covalently linked. A mutual prodrug allows each drug to act as a carrier for the other, delivering both drugs to their target sites. There are two main types of mutual prodrugs: carrier-linked prodrugs, where one drug is directly attached to the other; and bioprecursor prodrugs, which require chemical modification in vivo to release the active drugs. The objectives in designing mutual prodrugs are to improve drug delivery to target sites, provide synergistic effects, and reduce adverse effects. Several examples of mutual prodrugs from different therapeutic areas are provided, such as anti-tuberculosis,
Selection of excipients must be done with an utmost care to avoid physical and chemical interactions that ultimately lead to the degradation of the quality of the product.
Introduction to pharmacokinetics and pharmacodynamics 2022.docAhmed Ali
Studying pharmacology provides an understanding of drug interactions with living systems and their optimal medical use. Pharmacology deals with drugs obtained from natural, synthetic, and biotechnology sources. Drugs vary in properties like size, chemistry, and stereochemistry. They are named chemically, generically, and by proprietary names. Good drugs are selected based on effectiveness, safety, and other factors. A drug's clinical response depends on pharmacokinetic and pharmacodynamic variables. Adverse drug reactions can occur and are studied in toxicology. New drugs undergo extensive testing and regulatory approval processes. Pharmacodynamics concerns drug mechanisms of action through receptor interactions and relationships between drug concentrations and responses.
The document discusses the application of pharmacokinetics in new drug development and designing dosage forms. Pharmacokinetics helps understand how the body affects a drug after administration through absorption, distribution, metabolism and excretion. It is used in drug design, developing dosage regimens, and improving drug therapy. Pharmacokinetics principles can be applied to developing controlled release drugs and increasing bioavailability. Factors like lipophilicity and solubility affect drug absorption, and properties like volume of distribution and clearance impact half-life. Pharmacokinetics also aids in identifying metabolic pathways and drug-metabolizing enzymes. Protein binding influences pharmacokinetic properties and drug effects.
This document provides an introduction to veterinary pharmacology. It discusses key topics including:
1. Veterinary pharmacology is divided into pharmacokinetics, which is what the body does to a drug, and pharmacodynamics, which is what a drug does to the body.
2. Pharmacokinetics includes absorption, distribution, metabolism and excretion of drugs in the body. Pharmacodynamics involves drug receptors, effects, and toxicity.
3. Drugs can be classified by their chemical, generic or brand names. The chemical name provides the exact composition while the generic name is established when first manufactured.
The document discusses drug-excipient compatibility studies, which are important to understand interactions between active pharmaceutical ingredients and excipients. There are three main types of incompatibility - physical, chemical, and therapeutic. Compatibility studies help identify incompatible excipients, ensure excipients do not impact drug stability, and can help stabilize unstable drugs. Methods to study compatibility include thermal techniques like DSC, spectroscopic techniques, microscopy, and chromatography. The goal is to avoid issues with drug stability and efficacy during storage and use.
This document provides an overview of the Medicinal Chemistry MCHM 311 course at the International University of Africa's Faculty of Pharmacy. It discusses topics that will be covered in the course like principles of drug design, drug metabolism, and factors influencing drug metabolism. It also defines medicinal chemistry and discusses the history and key concepts of the discipline, including how drugs work by binding to receptors and the processes of drug discovery, design, and development.
Mechanism of drug action & factor modifying drug actionDipak Bari
This document discusses pharmacodynamics and the mechanisms of drug action. It explains that pharmacodynamics is the study of biochemical and physiological effects of drugs and their mechanisms of action. The key mechanisms discussed are: receptor-mediated binding, non-receptor mediated effects, enzyme inhibition or stimulation, and physical or chemical properties. Factors that can modify a drug's action like body weight, age, drug interactions, and tolerance are also summarized.
This document provides an overview of the key concepts in medicinal chemistry that will be covered in the class. It discusses the history and evolution of medicinal chemistry, defining drugs and their properties, drug discovery and design processes, and the pharmacokinetic and pharmacodynamic phases of drug action. The goal of medicinal chemistry is to design and synthesize new drug molecules through understanding their interactions with biological targets and structure-activity relationships.
Rational drug design begins by identifying a biological target implicated in disease. Drugs are then designed to modulate this target's activity in order to treat the disease. For a target to be suitable, there must be evidence it is disease-relevant and capable of binding small molecules. Once identified, the target is cloned, expressed, and purified. This allows high-throughput screening of chemical libraries to identify candidates that modify the target. Successful candidates should have properties predicting oral availability and low toxicity. Prodrugs and combinatorial chemistry are approaches that can improve drug properties and efficiency of discovery.
This document provides an overview of pharmacokinetics and its applications in drug development and clinical practice. It discusses how pharmacokinetics principles can help in designing new drugs with improved efficacy and safety, optimizing formulations, and developing controlled release products. It also describes how pharmacokinetics aids in understanding drug absorption, distribution, metabolism and excretion, which influences drug effects. Key applications include developing dosage regimens, addressing interactions, and conducting bioavailability/bioequivalence studies. Reference texts on biopharmaceutics and pharmacokinetics are also cited.
This document provides an overview of how pharmacokinetics principles can be applied in drug development and clinical practice. It discusses how pharmacokinetics helps in designing new drugs with improved efficacy and safety, optimizing formulations, and regulating drug dosing. Factors like absorption, distribution, metabolism and excretion that influence drug behavior in the body are considered. The effects of lipophilicity and solubility on absorption and ways to modify pharmacokinetic properties like half-life are summarized. References on biopharmaceutics and pharmacokinetics textbooks are also provided.
The document discusses ChemDraw, a molecule editor first created in 1985. It was later acquired by PerkinElmer. ChemDraw allows users to create and modify 2D and 3D representations of chemical structures. The document introduces ChemDraw and another similar program called ACD/ChemSketch. It also lists some features and search modes of ChemDraw but does not provide details. Links to video tutorials for ChemDraw and ChemSketch are included.
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in important biological processes like DNA synthesis and energy metabolism. It serves as a cofactor for enzymes involved in metabolic pathways. Vitamin B12 deficiency can cause neurological problems and megaloblastic anemia if left untreated. The chemical structure of vitamin B12 is complex, containing a corrin ring with a central cobalt ion. It is produced industrially through fermentation of microorganisms like Pseudomonas denitrificans or Propionibacterium shermanii.
Communication in Insects.
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Uses of Insect Pheromones.
Synthesis of Insect Pheromones.
Use of pheromones in insect pest management.
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This document provides information about High Performance Liquid Chromatography (HPLC) and Gas Chromatography. It discusses the basic principles, instrumentation, and applications of HPLC, including the types of columns, mobile phases, pumps, injectors, detectors, and data acquisition systems used. It also summarizes the basic principles of Gas Chromatography, where a gas mobile phase is used to separate components of a vaporized sample based on interactions with a stationary phase. Key applications of HPLC mentioned include pharmaceutical analysis, environmental monitoring, clinical analysis, and food and flavor analysis.
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Introduction, Basic Principles, Terminology, Instrumentation, Ionization techniques (EI, CI, FAB, MALDI, and ESI), Mass Analyzer (Magnetic sector instruments, Quadrupole, TOF, and ICR ), and Applications of Mass Spectrometry.
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Qualitative analysis of functional group
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Distinction between two types of hydrogen bonding
Study of chemical reaction
Study of Keto-Enol tautomerism
Conformational analysis
Geometrical isomerism
Study of complex molecules
Detection of impurity in a compound
Identification of the organic compounds by IR
Hydrocarbons, Aromatic compounds, Alcohol, Phenols, Ethers, Aldehydes, Ketones, Esters, Acid chlorides, Anhydrides, Amides, Amines, Nitriles, Isocynates, Isothiocynates, Imines and Nitro compounds.
Introduction
Instrumentation
Sampling techniques
Group frequencies
Factors affecting group frequencies
Complementarity of IR and Raman spectroscopy
Applications of Infrared spectroscopy
Introduction,Instrumentation, Classification of electronic transitions, Substituent and solvent effects, Classification of electronic transitions
Substituent and solvent effects
Applications of UV Spectroscopy
UV spectral study of alkenes
UV spectral study of poylenes
UV spectral study of α, β-unsaturated carbonyl
UV spectral study of Aromatic compounds
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Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
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Comparing the relative basicity of the nucleophile and the product is extremely helpful in determining how reversible the addition reaction is. Reactions with Grignards and hydrides are irreversible. Reactions with weak bases like halides and carboxylates generally don’t happen.
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hematic appreciation test is a psychological assessment tool used to measure an individual's appreciation and understanding of specific themes or topics. This test helps to evaluate an individual's ability to connect different ideas and concepts within a given theme, as well as their overall comprehension and interpretation skills. The results of the test can provide valuable insights into an individual's cognitive abilities, creativity, and critical thinking skills
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concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
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Drug discovery and design
1. Dr. BASAVARAJAIAH S. M.
Assistant Professor and Coordinator
P.G. Department of Chemistry
Vijaya College
Bangalore-560 004
BASICS CONCEPTS OF MEDICINAL
CHEMISTRY
2. Contents
DRUG DISCOVERY
Drug Discovery without a lead
LEAD DISCOVERY/IDENTIFICATION
LEAD MODIFICATION
CONCEPT OF PRODRUGS AND SOFT DRUGS
DRUG RECEPTOR INTERACTIONS
7. DRUG DISCOVERY
Drug discovery is a very time-consuming and expensive
process.
Estimates of the average time required to bring a drug to the
market range from 10-12 years and at an average cost of $600-
800 million.
For approximately every 10, 000 compounds that are evaluated
in animal studies, 10 will make it to human clinical trials in order to
get 1 compound on the market.
In general, drugs are not discovered. What is more likely
discovered is known as a lead compound.
8. The lead is a prototype compound that has a number of
attractive characteristics, such as the desired biological or
pharmacological activity, but may have other undesirable
characteristics, for example, high toxicity, other biological
activities, insolubility, or metabolism problems.
The structure of the lead compound is modified by synthesis
to amplify the desired activity and to minimize or eliminate the
unwanted properties to a point where a drug candidate.
Prior to lead discovery and lead modification, two common
drugs discovered without a lead are discussed.
13. LEAD DISCOVERY/IDENTIFICATION
Generally following steps are involved in lead discovery
1. Random screening
2. Non-random/Targeted/Focus screening
3. Drug metabolism studies
4. Clinical observations
5. Rational approaches
14. 1.RANDOM SCREENING
In the approach of known drugs and other compounds with
desired activity, a random screen is a valuable approach.
Random screening involves n intellectualization; all compounds
are tested in the bioassay without regard to their structures.
This is the lead discovery method of choice when nothing is
known about the receptor target.
Streptomycin Tetracycline
15. 2. NON-RANDOM/TARGETED/FOCUS SCREENING
Non-random screening is a more narrow approach than is
random screening.
In this case, compounds having a vague resemblance to weakly
active compounds uncovered in a random screen.
Random screen was modified to a nonrandom screen because
of budgetary and manpower restrictions.
16. 3. DRUG METABOLISM STUDIES
During drug metabolism studies, metabolites that are isolated are
screened to determine if the activity observed is derived from the
drug candidate or from a metabolite.
Sulindac Reduced form
(Antinflammatory agent)
17. 4. CLINICAL OBSERVATIONS
Sometimes a drug candidate during clinical trials will exhibit
more than one pharmacological activity; it may produce side
effect.
This compound, then, can be used as a lead for the secondary
activity.
Dimenhydrinate (Antihistamine) after clinical observations
showing that treatment for motion sickness.
Bupropion is a antidepressant drug, Clinical
studies showed that smoking Cessation aid.
18. 5. RATIONAL APPROACHES
Rational approaches to drug design now have become the
major routes to lead discovery.
The knowledge about the receptors and their mode of
interaction with drug molecules plays am important role in drug
design.
This idea maybe used to develop confirmationally bioactive
skeletons having exact three dimensional complementarity to a
receptor.
Greater potency, higher selectivity and less adverse effects are
expected by reducing the flexibility of the drug structure.
19. Serotonin Indomethacin
Ex.1: Serotonin was used as lead for anti-inflammatory agents,
and from this drug Indomethacin was developed.
Progesterone
17- Ethinyl estradiol
Norgestrel
Contraceptive drug
Ex.2:
20.
21. Any drug molecule consists of both, essential and non-essential
parts.
Essential part governing the pharmacodynamics property (D-R
interactions).
Non-essential part governing the pharmacokinetics property
(ADME).
The schematic representation of nature of such bioactive
functional groups along with their inter-atomic distance is known
as pharmacophore.
1. IDENTIFICATION OF ACTIVE PART (PHARMACOPHORE)
22. Auxophore: Other atoms in the lead molecule, may be
extraneous which may be interfering with the binding of
pharmacophore.
Structural modification can be done to improve pharmacokinetic
properties of the drugs.
For example: The presence of a phenyl ring, asymmetric
carbon, ethylene bridge, and tertiary nitrogen are found to be
minimum structural requirements for a narcotic analgesic to
become active.
24. 2. FUNCTIONAL GROUP OPTIMIZATION
The activity of a drug can be correlated to its structure in terms
of the contribution of its functional groups to liphophilicity,
electronic and steric factors.
Hence, by selecting proper functional groups, one can govern
the drug distribution pattern and can avoid the occurrence of side
effects.
Chlorothiazide
Dazoxide
Only Antihypertensive activity Antihypertensive activity
Diuretic activity
25.
26. 3. Structure-Activity Relationship (SAR)
Structure-Activity Relationship (SAR) studies usually
involves the interpretation of activity in terms of the
structural features of a drug molecules.
27. Ex: SAR studies of Sulfonamides drugs
The following conclusions are made;
45. 2. Effect of ionization:
Electronic effects:- The Hammett equations
46.
47.
48.
49.
50.
51.
52. CONCEPT OF PRODRUGS AND SOFT DRUGS
PRODRUGS
A prodrug is a inactive compound that is converted into an
active drug by a metabolic biotransformation (Usually hydrolysis).
Instead of administering a drug directly, a corresponding
prodrug can be used to improve how the drug is absorbed,
distributed, metabolized, and excreted (ADME).
Prodrugs are often designed to improve bioavailability when a
drug itself is poorly absorbed from the gastrointestinal tract.
PRODRUG DRUG
Invivo
53. Ex:
Aspirin Methyl salicylate Phenyl salicylate
All the above 3 compounds (prodrugs) on hydrolysis give
salicylic acid (Active drug).
In order to state that prodrug formation has occurred, evidence
must be provided that original drug has been liberated in vivo.
The prodrug is not responsible for the activity and should be
benefit of biological activity.
54. PRODRUG DESIGN or DRUG LATENTIATION
There are 3 main phases of drug action, namely,
The pharmaceutical (Formulation).
The Pharmacodynamic (Drug-Receptor Interactions).
Pharmacokinetics (ADME)
Problems exist in all three phases.
Prodrug formation seeks to address the problem in the
pharmaceutical and pharmacokinetic phases.
It does not address the Pharmacodynamic phase problems.
Drug latentiation is the chemical modification of a biologically
active compound to form a new compound, which in vivo will
liberate the parent compound.
55. These drawbacks includes;
Unpleasant taste and odor
High acidity
Poor hydrophilic
Instability
Shorter duration of action
Site non-specificity
Poor absorption-distribution
Less attractive color
Prodrug designing is required to overcome these problems.
62. 1. Non-intentional prodrug:
Sometimes, after administration of the drug the metabolic
studies indicate the prodrug nature of drug.
It becomes accidentally evident that the activity of a drug is
because of its metabolite and not because of the parent drug.
Sulindac (Prodrug) Reduced form (Drug)
(Antinflammatory agent)
73. SOFT DRUGS
Soft drugs (antedrugs) are biologically active drugs designed to
have a predictable and controlled metabolism.
Soft drugs are metabolism to nontoxic and inactive products
after they have achieved their desired pharmacological effect.
Ex: Drugs acting on specific areas in the eye, brain and testes
etc.
74. ADVANTAGES OF SOFT DRUGS
Elimination of toxic metabolites, thereby increasing the
therapeutic index of the drug.
Avoidance of pharmacologically active metabolites that can lead
to long term effects.
Elimination of drug interactions resulting from metabolite
inhibition of enzymes.
Simplification of pharmacokinetic problems cause by multiple
active species.
75. PROPERTIES OF SOFT DRUGS
It has close structural similarity to the lead.
It is a metabolically sensitive moiety built into the lead structure.
The sensitive part does not affect the overall physiochemical or
steric properties of the lead compound.
Soft drug metabolism rate can be predictable and controllable.
Metabolic products of soft drugs are nontoxic and have no
other biological activities.
Soft drug metabolic products does not give to highly reactive
intermediates.
76.
77. HARD DRUGS
Hard drugs are nonmetabolizable compounds, characterized
either by high lipid solubility.
They are poor substrates for the metabolizing enzymes.
They bind strongly to receptor site and do not easily excreted
out of the system.
When they excrete, they destroy the receptor sites.
Continous usage of hard drugs leads to addiction.
Heroin Nimesulide
78. ANALOGS
Analog design is usually defined as the modification of a drug
molecule or of any bioactive compound in order to prepare a new
molecule showing chemical and biological similarity with the
original model compound.
Analogs are primarily prepared synthetically to increase the
potency of the original drug or resistance of the parental drug.
Pencillin G
Amipicillin Amoxyllin
94. OCCUPANCY THEORY
Proposed by Gaddum and Clark.
The intensity of the pharmacological effect is directly
proportional to the number of receptors occupied by the drug.
The pharmacological response of a drug molecule is a function
of dose, number of receptor available and its intrinsic activity.
The rate of combination of drug and receptor can therefore be
expressed as; K1 [R] [A]
Where K1 = Association constant R= Concentration of
unoccupied receptor, A= Concentration of drug.
95. Similarly, K2 [RA]
Where K2 = Dissociation constant RA= Concentration of
occupied receptor, A= Concentration of drug.
At equilibrium,
K1 [R] [A]= K2 [RA]
If [R] + [RA] = r (Concentration of receptor) &
K2/K1=KA (Eq. constant)
When RA=r ie all the receptors are occupied and the response is
thus proportional to its intrinsic activity (Xn or ).
96. Drawbacks:
This theory does not account for partial agonist and antagonist.
Ariens and Stephenson modified the occupancy theory to
account for partial agonist.
They coined the terms affinity and efficacy/intrinsic activity.
It does not account for why two drugs that can occupy the same
receptor can act differently i.e. one as an agonist, the other as an
antagonist.
97. RATE THEORY
Paton and Rang proposed the rate theory.
They proposed that the activation of receptors is proportional to
the total number of encounters of the drug with its receptor per
unit time.
Therefore, the rate theory suggests that the pharmacological
activity is a function of the rate of association and dissociation of
the drug with the receptor, and not the number of occupied
receptors.
Each association would produced a quantum of stimulus.
In the case of agonists, the rate of association is slow and
dissociation rate would be fast.
98. In the case of antagonist, the rate of association is fast and
dissociation rate would be slow.
At equilibrium, the occupancy and rate theory mathematically
equivalent.
As in the case of the occupancy theory, the rate theory does not
rationalize why the different types of compounds exhibit the
characteristics that they do.
99. INDUCED FIT THEORY
The induced fir theory of Koshland was originally proposed for
the action of substrates and enzymes, but it could apply to drug-
receptor interaction as well.
According to this theory the receptor need not necessarily exist
in the appropriate conformation required to bind the drug.
As the drug approaches the receptor, a conformational change
is induced that orients the essential binding sites.
The conformational change in the receptor could be responsible
for the initiation of the biological response.
The receptor was suggested to be elastic, and it could return to
its original conformation after the drug was release.
100. The conformational change need not occur only in the receptor;
the drug also could undergo deformation.
According to this theory, an agonist would induce a
conformational change and elicit a response.
An antagonist would bind without a conformational change.
A partial agonist would cause a partial conformational change.
101. MACROMOLECULAR PERTURBATION THEORY
Belleau suggested that in the interaction of a drug with a
receptor two general types of macromolecular perturbations could
result;
Specific perturbations –Biological response (Agonist).
Non-specific perturbations –No biological response (Antagonist).
This theory offers a physicochemical basis for the rationalization
of molecular phenomena that involve receptors.
This theory does not address the concept of inverse agonism.