The document discusses the process of drug discovery, including target selection, lead discovery, medicinal chemistry, in vitro and in vivo studies, and clinical trials. Target selection involves identifying cellular or genetic targets involved in disease through techniques like genomics, proteomics, and bioinformatics. Lead discovery focuses on identifying small molecule modulators of protein function through methods like synthesis, combinatorial chemistry, assay development, and high-throughput screening. Medicinal chemistry then works to optimize these leads. [/SUMMARY]
Drug discovery and development is a long, expensive, and complex process averaging about 12 years and $500 million to bring a new prescription medication to market. Only 1 in 10,000 compounds eventually becomes an approved drug. The process involves discovery, preclinical research, clinical trials, and regulatory approval. Discovery aims to identify candidate drug molecules, while preclinical research studies their safety and efficacy in animal models before human testing. Clinical trials then evaluate new drugs with patients for safety and effectiveness over several phases before regulatory approval and marketing.
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.
This document outlines the stages of drug development, beginning with drug discovery and ending with regulatory approval. It discusses the history of drug development from ancient times to modern pharmaceutical industry. The key stages are described as pre-clinical development involving non-human testing, clinical development involving human trials to test safety and efficacy, and regulatory approval. Drug discovery involves target identification, validation, lead discovery through screening, and lead optimization to improve desired properties. Recent advances like genomics, high-throughput screening, and bioinformatics have accelerated the drug development process.
A presentation outlining the various processes a chemical compound undergoes (thorough & rigorous screening procedures) before it is finally introduced into the drug market
Rational drug design is a process that begins with knowledge of a biological target and aims to design small molecules that interact optimally with that target to produce a desired therapeutic effect. It involves analyzing the structures of active molecules and known targets, then designing new molecules that are predicted to specifically fit the target. This may involve modifying existing lead compounds or building new ones de novo. The goal is to develop drugs with greater potency, selectivity and fewer side effects than those found by traditional trial-and-error means. Cimetidine for reducing stomach acid is provided as an example of rational drug design, where histamine analogs were synthesized and optimized until an effective and safe product was obtained.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
This document provides an overview of high throughput screening (HTS). It defines HTS as a process that can quickly screen 10,000-100,000 compounds per day to identify interactions between chemicals and biological targets. The document outlines the history, definitions, instrumentation, techniques, applications and limitations of HTS. HTS is an important tool in drug discovery for identifying hit compounds from libraries that can then be optimized into lead molecules.
Drug discovery and development is a long, expensive, and complex process averaging about 12 years and $500 million to bring a new prescription medication to market. Only 1 in 10,000 compounds eventually becomes an approved drug. The process involves discovery, preclinical research, clinical trials, and regulatory approval. Discovery aims to identify candidate drug molecules, while preclinical research studies their safety and efficacy in animal models before human testing. Clinical trials then evaluate new drugs with patients for safety and effectiveness over several phases before regulatory approval and marketing.
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.
This document outlines the stages of drug development, beginning with drug discovery and ending with regulatory approval. It discusses the history of drug development from ancient times to modern pharmaceutical industry. The key stages are described as pre-clinical development involving non-human testing, clinical development involving human trials to test safety and efficacy, and regulatory approval. Drug discovery involves target identification, validation, lead discovery through screening, and lead optimization to improve desired properties. Recent advances like genomics, high-throughput screening, and bioinformatics have accelerated the drug development process.
A presentation outlining the various processes a chemical compound undergoes (thorough & rigorous screening procedures) before it is finally introduced into the drug market
Rational drug design is a process that begins with knowledge of a biological target and aims to design small molecules that interact optimally with that target to produce a desired therapeutic effect. It involves analyzing the structures of active molecules and known targets, then designing new molecules that are predicted to specifically fit the target. This may involve modifying existing lead compounds or building new ones de novo. The goal is to develop drugs with greater potency, selectivity and fewer side effects than those found by traditional trial-and-error means. Cimetidine for reducing stomach acid is provided as an example of rational drug design, where histamine analogs were synthesized and optimized until an effective and safe product was obtained.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
This document provides an overview of high throughput screening (HTS). It defines HTS as a process that can quickly screen 10,000-100,000 compounds per day to identify interactions between chemicals and biological targets. The document outlines the history, definitions, instrumentation, techniques, applications and limitations of HTS. HTS is an important tool in drug discovery for identifying hit compounds from libraries that can then be optimized into lead molecules.
This document discusses high throughput screening and cell-based assays. It begins by defining high throughput screening as a process used in drug discovery to quickly assay a large number of compounds against a biological target to identify hits or leads. It then describes some key aspects of high throughput screening methodology including detection methods like spectroscopy, chromatography, and microscopy. The document outlines the advantages of cell-based assays compared to biochemical assays, noting they provide a more accurate representation using live cells. Finally, it defines the key elements of a cell-based assay as having a cellular component, a target molecule, an instrument, and informatics for data analysis.
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.
- Biosimilars are biologic medical products that are similar but not identical copies of original biologic drugs. They are developed when the patent expires on the original product.
- Regulatory agencies have stringent approval criteria for biosimilars to demonstrate similar quality, safety and efficacy as the reference product. Clinical trials must show comparable pharmacokinetics, pharmacodynamics and immunogenicity.
- While biosimilars increase access and lower costs, they are not generic copies and have unique safety profiles. Automatic substitution is not appropriate and unique nonproprietary names and labeling is required to facilitate pharmacovigilance.
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 document discusses the economics of drug discovery. It notes that drug discovery takes 3-20 years and costs several billion to tens of billions of dollars. The process involves determining the causes of diseases and finding compounds for treatment. Drugs then undergo pre-clinical and clinical trials, with the three phases of clinical trials costing upwards of $100 million alone. A new 2020 study estimated the median cost of getting a new drug to market is $985 million, with the average being $1.3 billion. This is lower than previous estimates of $2.8 billion. The document also outlines the present costs involved in various stages of drug discovery and development.
High Throughput Screening (HTS) is a drug discovery process that uses automation to quickly assay a large number of compounds against biological or biochemical targets to identify potential drug candidates. Key aspects of HTS include testing compounds in microtiter plates with 96, 384, or 1536 wells using assays like cell-based, enzyme, or tissue response tests. HTS allows for high speed, sensitivity, and reproducibility in screening large libraries of compounds cost effectively. Detection methods used in HTS include spectroscopy, chromatography, calorimetry, and microscopy.
Target identification, target validation, lead identification and lead
Optimization.
• Economics of drug discovery.
• Target Discovery and validation-Role of Genomics, Proteomics and
Bioinformatics.
• Role of Nucleic acid microarrays, Protein microarrays, Antisense
technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins.
• Role of transgenic animals in target validation.
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.
DRUG DISCOVERY & DEVELOPMENT PROCESS, it's a detail description about how drug is made available in market it's development and discovery of drug The Hole Study is given in This Topic.
The document provides an overview of the drug discovery and development process. It discusses the various stages involved, including target selection using genomics, proteomics and bioinformatics; lead discovery through synthesis, isolation and high-throughput screening; medicinal chemistry such as structure-activity relationships studies; in vitro and preclinical in vivo testing in animal models; and clinical trials in humans. The timeline for this process can span over 10-15 years from drug target identification to regulatory approval. Key techniques and approaches at each stage are also summarized.
Target Validation
Introduction,Drug discovery, Target identification and validation, Target validation and techniques
By
Ms. B. Mary Vishali
Department of Pharmacology
The document outlines the phases of clinical trials:
- Phase 0 involves microdosing to determine pharmacokinetics and pharmacodynamics.
- Phase 1 studies a drug's safety on 20-100 healthy volunteers and finds the optimal dose.
- Phase 2 trials on 100-300 people study a drug's biological effects and continues safety monitoring. It has two types: 2a determines dosing and 2b is pivotal, blinded, and multicenter.
- Phase 3 are large randomized controlled trials on 300-3000 people comparing a drug to standard treatment. It has two types: 3a tests different indications and 3b continues trials pending regulatory approval.
- Phase 4 occurs after approval to detect rare adverse effects
This document discusses the key steps in the drug discovery process, including target identification and validation, lead identification, and lead optimization. It describes how identifying the biological target of a disease is the first step, followed by validating that target. Leads are then identified, which are compounds that show desired biological activity against the validated target. The leads undergo optimization to improve properties like potency. Methods for target identification, lead identification, and lead optimization are also outlined.
Drug discovery and development is and always has been the most exciting part of clinical pharmacology. It is my attempt to compile the basic concepts from various books, articles and online journals. Feel free to comment.
Target identification in drug discoverySwati Kumari
The document discusses target identification in drug discovery. It begins by defining a target and explaining that target identification is the first step in drug discovery. It then discusses various approaches to target identification, including direct biochemical methods, genetic interaction methods, and computational inference methods. The document also discusses characteristics of drug targets and how drugs interact with targets at the molecular level. It provides examples of tools that can be used for target identification and validation, such as microarrays, antisense technology, and proteomics. In summary, the document outlines the process of target identification in drug discovery and various methods that can be used to identify and validate potential drug targets.
Genomics, proteomics, and bioinformatics are important fields that help advance drug development. Genomics studies entire genomes and can identify disease-associated genes. Proteomics identifies the proteins expressed in a sample and how they differ between healthy and diseased tissues. Bioinformatics uses computers to store and analyze biochemical and biological data, especially related to genomics. These fields help discover new drug targets, validate existing targets, select drug candidates, study mechanisms of action and toxicity. Integrating omics data from genomics to proteomics provides a more comprehensive understanding of biological systems compared to individual fields alone.
Genomics and proteomics in drug discovery and developmentSuchittaU
This document discusses the role of genomics and proteomics in drug discovery and development. It explains that genomics and proteomics technologies can help identify new drug targets by comparing gene and protein expression between healthy and diseased cells. Proteomics in particular analyzes changes in protein levels and can quantify individual proteins using techniques like 2D gel electrophoresis and mass spectrometry. The integration of genomics and proteomics provides a more comprehensive understanding of biological systems and is improving the drug discovery process.
The drug development process involves several phases of clinical trials overseen by regulatory agencies. Drugs must first show safety in pre-clinical animal and lab testing before entering human trials. Clinical trials involve 3 phases - Phase I tests safety in small groups, Phase II assesses efficacy and optimal dosing in larger groups of patients, and Phase III confirms efficacy in even larger groups. If results are positive, the drug company submits a New Drug Application to the regulatory agency which can take 2-3 years to review before approving the drug for the market. Post-market studies in Phase IV further monitor long-term safety and efficacy. The entire process from discovery to market approval takes an average of 10-15 years and over $1 billion
Drug development involves rigorous pre-clinical and clinical testing to prove a drug is safe and effective. Pre-clinical testing involves laboratory and animal studies. Clinical trials in humans have four phases, with each subsequent phase involving more subjects to further evaluate safety, efficacy, and optimal dosage. After Phase III trials demonstrate a drug's benefits outweigh its risks, a New Drug Application is submitted to regulators for review. If approved, Phase IV trials continue monitoring the drug's long-term safety profile after market approval. The entire process from discovery to market approval takes an average of 8-12 years and costs $800-900 million.
This document discusses high throughput screening and cell-based assays. It begins by defining high throughput screening as a process used in drug discovery to quickly assay a large number of compounds against a biological target to identify hits or leads. It then describes some key aspects of high throughput screening methodology including detection methods like spectroscopy, chromatography, and microscopy. The document outlines the advantages of cell-based assays compared to biochemical assays, noting they provide a more accurate representation using live cells. Finally, it defines the key elements of a cell-based assay as having a cellular component, a target molecule, an instrument, and informatics for data analysis.
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.
- Biosimilars are biologic medical products that are similar but not identical copies of original biologic drugs. They are developed when the patent expires on the original product.
- Regulatory agencies have stringent approval criteria for biosimilars to demonstrate similar quality, safety and efficacy as the reference product. Clinical trials must show comparable pharmacokinetics, pharmacodynamics and immunogenicity.
- While biosimilars increase access and lower costs, they are not generic copies and have unique safety profiles. Automatic substitution is not appropriate and unique nonproprietary names and labeling is required to facilitate pharmacovigilance.
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 document discusses the economics of drug discovery. It notes that drug discovery takes 3-20 years and costs several billion to tens of billions of dollars. The process involves determining the causes of diseases and finding compounds for treatment. Drugs then undergo pre-clinical and clinical trials, with the three phases of clinical trials costing upwards of $100 million alone. A new 2020 study estimated the median cost of getting a new drug to market is $985 million, with the average being $1.3 billion. This is lower than previous estimates of $2.8 billion. The document also outlines the present costs involved in various stages of drug discovery and development.
High Throughput Screening (HTS) is a drug discovery process that uses automation to quickly assay a large number of compounds against biological or biochemical targets to identify potential drug candidates. Key aspects of HTS include testing compounds in microtiter plates with 96, 384, or 1536 wells using assays like cell-based, enzyme, or tissue response tests. HTS allows for high speed, sensitivity, and reproducibility in screening large libraries of compounds cost effectively. Detection methods used in HTS include spectroscopy, chromatography, calorimetry, and microscopy.
Target identification, target validation, lead identification and lead
Optimization.
• Economics of drug discovery.
• Target Discovery and validation-Role of Genomics, Proteomics and
Bioinformatics.
• Role of Nucleic acid microarrays, Protein microarrays, Antisense
technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins.
• Role of transgenic animals in target validation.
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.
DRUG DISCOVERY & DEVELOPMENT PROCESS, it's a detail description about how drug is made available in market it's development and discovery of drug The Hole Study is given in This Topic.
The document provides an overview of the drug discovery and development process. It discusses the various stages involved, including target selection using genomics, proteomics and bioinformatics; lead discovery through synthesis, isolation and high-throughput screening; medicinal chemistry such as structure-activity relationships studies; in vitro and preclinical in vivo testing in animal models; and clinical trials in humans. The timeline for this process can span over 10-15 years from drug target identification to regulatory approval. Key techniques and approaches at each stage are also summarized.
Target Validation
Introduction,Drug discovery, Target identification and validation, Target validation and techniques
By
Ms. B. Mary Vishali
Department of Pharmacology
The document outlines the phases of clinical trials:
- Phase 0 involves microdosing to determine pharmacokinetics and pharmacodynamics.
- Phase 1 studies a drug's safety on 20-100 healthy volunteers and finds the optimal dose.
- Phase 2 trials on 100-300 people study a drug's biological effects and continues safety monitoring. It has two types: 2a determines dosing and 2b is pivotal, blinded, and multicenter.
- Phase 3 are large randomized controlled trials on 300-3000 people comparing a drug to standard treatment. It has two types: 3a tests different indications and 3b continues trials pending regulatory approval.
- Phase 4 occurs after approval to detect rare adverse effects
This document discusses the key steps in the drug discovery process, including target identification and validation, lead identification, and lead optimization. It describes how identifying the biological target of a disease is the first step, followed by validating that target. Leads are then identified, which are compounds that show desired biological activity against the validated target. The leads undergo optimization to improve properties like potency. Methods for target identification, lead identification, and lead optimization are also outlined.
Drug discovery and development is and always has been the most exciting part of clinical pharmacology. It is my attempt to compile the basic concepts from various books, articles and online journals. Feel free to comment.
Target identification in drug discoverySwati Kumari
The document discusses target identification in drug discovery. It begins by defining a target and explaining that target identification is the first step in drug discovery. It then discusses various approaches to target identification, including direct biochemical methods, genetic interaction methods, and computational inference methods. The document also discusses characteristics of drug targets and how drugs interact with targets at the molecular level. It provides examples of tools that can be used for target identification and validation, such as microarrays, antisense technology, and proteomics. In summary, the document outlines the process of target identification in drug discovery and various methods that can be used to identify and validate potential drug targets.
Genomics, proteomics, and bioinformatics are important fields that help advance drug development. Genomics studies entire genomes and can identify disease-associated genes. Proteomics identifies the proteins expressed in a sample and how they differ between healthy and diseased tissues. Bioinformatics uses computers to store and analyze biochemical and biological data, especially related to genomics. These fields help discover new drug targets, validate existing targets, select drug candidates, study mechanisms of action and toxicity. Integrating omics data from genomics to proteomics provides a more comprehensive understanding of biological systems compared to individual fields alone.
Genomics and proteomics in drug discovery and developmentSuchittaU
This document discusses the role of genomics and proteomics in drug discovery and development. It explains that genomics and proteomics technologies can help identify new drug targets by comparing gene and protein expression between healthy and diseased cells. Proteomics in particular analyzes changes in protein levels and can quantify individual proteins using techniques like 2D gel electrophoresis and mass spectrometry. The integration of genomics and proteomics provides a more comprehensive understanding of biological systems and is improving the drug discovery process.
The drug development process involves several phases of clinical trials overseen by regulatory agencies. Drugs must first show safety in pre-clinical animal and lab testing before entering human trials. Clinical trials involve 3 phases - Phase I tests safety in small groups, Phase II assesses efficacy and optimal dosing in larger groups of patients, and Phase III confirms efficacy in even larger groups. If results are positive, the drug company submits a New Drug Application to the regulatory agency which can take 2-3 years to review before approving the drug for the market. Post-market studies in Phase IV further monitor long-term safety and efficacy. The entire process from discovery to market approval takes an average of 10-15 years and over $1 billion
Drug development involves rigorous pre-clinical and clinical testing to prove a drug is safe and effective. Pre-clinical testing involves laboratory and animal studies. Clinical trials in humans have four phases, with each subsequent phase involving more subjects to further evaluate safety, efficacy, and optimal dosage. After Phase III trials demonstrate a drug's benefits outweigh its risks, a New Drug Application is submitted to regulators for review. If approved, Phase IV trials continue monitoring the drug's long-term safety profile after market approval. The entire process from discovery to market approval takes an average of 8-12 years and costs $800-900 million.
The document discusses Investigational New Drug Applications (INDs), which are required for clinical trials of new drugs. It outlines the key components of an IND, including an introductory statement, investigator's brochure, protocols, chemistry/manufacturing information, and previous human experience. It also describes IND amendments, annual reports, and the roles of the sponsor and investigator. The overall purpose of an IND is to provide information to the FDA on a new drug's safety before it can be tested in humans.
The document discusses the key stages in the drug discovery and development process including target selection, compound screening and hit optimization, selecting a drug candidate through further optimization of properties like absorption and metabolism, safety testing in animals and humans, proof of concept clinical trials in patients, large phase 3 clinical trials for registration and approval, and finally launch and life cycle management. It notes that the entire process from discovery to approval can take 12-16 years and cost over $1 billion.
Drug discovery process style 5 powerpoint presentation templatesSlideTeam.net
The document describes the key stages in the drug discovery process, including cellular and genetic target identification, compound synthesis and isolation, high-throughput screening, lead optimization, preclinical testing in animal models and in vitro/in vivo studies, and clinical trials in humans. The flow diagram shows the iterative process moving from early research to identify biological targets through compound development and testing, culminating in clinical evaluation and potential approval of new therapeutics.
Drug Development Life Cycle - Costs and RevenueRobert Sturm
Presentation explains the Drug Development Process in terms of time/costs from initial research to final manufacturing. It presents strategies for increasing profits/decreasing costs, shows the impact of generics and details how Information Technology fits into this equation. It uses research from DiMasi and Grabowski to identify drug costs and product revenue.
Thyroid Hormone Disorders lecture :-
-Thyroid gland & Thyroid hormones.
-How does Thyroid hormone is formed ?
-Regulation of secretion.
-Hypothyroidism.
-Treatment of hypothyroidism .
-Administration of Levothyroxin.
-Levothyroxin interactions.
-Levothyroxin cautions.
-Hyperthyroidism .
-Symptoms & treatment of Hyperthyroidism.
-Removal of part or all of the thyroid.
-Blockade of hormone release .
-Inhibition of thyroid hormone synthesis.
-Mechanism of action of antithyroid.
-Administration of antithyroid drugs.
-Antithyroid drugs interactions.
-Antithyroid drugs cautions.
-General notes.
-Practical notes on levothyroxin.
-Practical notes on antithroid drugs.
-Rapid review.
-Test yourself.
The document discusses drug design, development, and delivery. It covers rational drug design using molecular properties and receptor modeling. Computer-assisted drug design uses molecular docking and QSAR methods. Neural networks are also used in drug design. Drug discovery involves identifying candidates and screening for efficacy. Drug development evaluates ADME, toxicity, and safety through preclinical and clinical studies. Drug delivery methods aim to effectively administer pharmaceutical compounds and improve drug release profiles.
This document provides an overview of parsimony methods for phylogenetic tree analysis. It defines key terms like rooted vs unrooted trees and describes the basic steps of parsimony analysis. Parsimony methods infer the phylogenetic tree that requires the fewest evolutionary changes to explain the observed similarities and differences in species' characteristics. The analysis proceeds by identifying informative sites in a sequence alignment, calculating the number of character changes on possible trees, and selecting the tree with the smallest number of changes as the most likely phylogenetic tree.
This document provides an overview of the history and methods of drug discovery, including traditional and computer-aided approaches. It discusses the traditional drug discovery life cycle from hit identification through random screening and the use of natural products and synthetic chemicals. It then introduces computer-aided drug design (CADD) and describes how it can be used throughout the drug discovery process, including structure-based design, ligand-based design, and de novo design to speed up screening and enable more rational drug design. It also lists some advantages of CADD over traditional methods and examples of drugs successfully developed using these approaches.
The document discusses the hit to lead (H2L) stage of drug discovery. In this stage, small molecule hits identified from high-throughput screening undergo limited optimization to identify lead compounds with improved binding affinity, selectivity, metabolic properties, and other qualities. The goal is to progress compounds from the micromolar binding range to nanomolar binding through synthetic analogs before advancing to the lead optimization stage. Key aspects of H2L include hit confirmation, expansion through synthetic analogs, and selection of lead series based on various criteria for further exploration.
Drug discovery process style 3 powerpoint presentation templatesSlideTeam.net
The document summarizes the key steps in the drug discovery process. It involves:
1) Identifying a biological target molecule through genomic research and functional analysis of genes.
2) Discovering seed lead compounds through high-throughput screening and combinatorial chemistry.
3) Scrutinizing drug candidates through estimation of efficacy, safety evaluation, pharmacokinetics studies, and manufacturing development.
4) Conducting clinical studies and applying for a new drug approval.
Systems Pharmacology 1: Drug re-positioning predictionAli Kishk
This document discusses drug repositioning prediction through systems pharmacology. It describes obtaining gene expression profiles from drugs in the LINCS database and using enrichment analysis to predict new disease indications. Specifically, it provides steps to get downregulated genes for a drug from LINCS Canvas Browser, then use Enrichr to analyze enriched diseases based on those genes. A demo is shown obtaining salbutamol's gene list and analyzing enriched diseases. The output includes top enriched diseases and shared genes between the input list and each disease.
Drug discovery process powerpoint presentation slides ppt templatesSlideTeam.net
The document describes the drug discovery process. It involves 10,000 to 20,000 candidate drugs undergoing discovery and screening. Promising candidates then undergo lead optimization using combinatorial chemistry and structure-based drug design. Finally, drugs must pass ADMET studies and clinical trials to receive FDA approval and reach the market.
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.
In Vitro ADMET Considerations for Drug Discovery and Lead GenerationOSUCCC - James
This document provides an overview of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays that are used during drug discovery and development. Key points:
- In vitro assays are designed to mimic what happens to a compound in vivo and provide early data on absorption, distribution, metabolic transformations, potential toxicity, and more.
- Common assays examine solubility, permeability, protein binding, metabolic stability, metabolism pathways, toxicity, and effects of transporters and drug-drug interactions.
- The data generated from these assays are used throughout the drug development process to inform compound selection, design better candidates, and identify liabilities early. Understanding a compound's properties helps optimize the likelihood of success
Repositioning Old Drugs For New Indications Using Computational ApproachesYannick Pouliot
Topiramate was identified as a potential drug candidate for inflammatory bowel disease (IBD) using a computational approach. Gene expression profiles of drugs and disease states were analyzed to find drugs that induced the reciprocal signature of IBD tissues compared to normal tissues. Topiramate decreased diarrhea in a rat model of IBD and counter-expressed genes observed in microarray data. This provides proof that drugs affecting gene expression anti-correlated to disease patterns may treat symptoms.
This document discusses the process of finding a lead compound in drug discovery. It describes the key steps as: 1) Choosing the disease to target. Factors like prevalence and market size are considered. 2) Choosing a drug target like a receptor or enzyme involved in the disease. Specificity and selectivity are important. 3) Identifying a bioassay or test to evaluate compounds, including in vitro and in vivo tests. High throughput screening allows testing many compounds quickly. 4) Finding a lead compound through various methods like screening natural products, existing drugs, combinatorial libraries, or computer-aided design. The goal is to discover compounds with the desired activity to use as a starting point for drug development.
The document discusses Signals' approach to drug repositioning using big data. It introduces Signals and their product intelligence expertise. Their solution automatically produces and delivers business analytics by collecting, integrating and analyzing big data from open web sources. The presentation discusses the challenges in drug development, need for repositioning, and Signals' evidence-based data model and methodology for characterizing a drug and generating queries to identify novel opportunities for increasing its ROI by detecting similar drugs, modifications, conditions and genomic data.
This document summarizes key points from a lecture on research and development (R&D). It discusses best practices in innovation including understanding customer needs, culture of innovation, open innovation, funding R&D, execution, creativity, and intellectual property protection. It provides definitions of R&D, describes the different types of R&D activities from basic research to development. It also discusses integrating R&D with corporate strategy, classifying R&D activities across industries, and the importance of strategic R&D planning and developing a technology portfolio.
Drugdiscoveryanddevelopment by khadga rajKhadga Raj
The document provides information on various stages of drug discovery and development, including target selection, lead discovery, medicinal chemistry, and clinical trials. It discusses techniques used at each stage such as genomics, proteomics, and bioinformatics for target identification. Key aspects of lead discovery like library development, SAR studies, and high-throughput screening are described. The roles of medicinal chemistry, in vitro and in vivo studies in optimizing leads into drug candidates are also summarized.
The document provides an overview of the drug discovery process. It discusses the various stages involved including target selection, lead discovery, medicinal chemistry, in vitro studies, in vivo studies, and clinical trials.
Target selection involves identifying biological targets implicated in disease through methods like genomics, proteomics, and bioinformatics. Lead discovery focuses on identifying small molecule modulators through synthesis, combinatorial chemistry, assay development, and high-throughput screening. Medicinal chemistry optimizes leads through approaches such as library development, SAR studies, in silico screening, and chemical synthesis. In vitro and in vivo studies evaluate drug candidates prior to clinical trials in humans.
Introduction to the drug discovery processThanh Truong
This document discusses the drug discovery process from target identification through FDA approval. It describes methods used for target identification such as genomics, bioinformatics, and proteomics. The stages of lead identification through high-throughput screening and structure-based drug design are outlined. Key aspects of lead optimization like characterizing potency, efficacy, pharmacokinetics, and toxicity are summarized. Details are provided on preclinical and clinical trial phases from Phase 0 through Phase IV post-marketing surveillance. Factors contributing to the declining drug approval rate like increased safety demands are noted. The high costs and failure rates associated with drug development are highlighted.
The document is an assignment on drug discovery and development submitted by Mary Melna to Prof. N.S. Harinarayan. It contains definitions of key terms like drug and the drug discovery and development processes. It then discusses the history of drug discovery from the 1920s onwards and timelines for drug discovery, development and FDA review. The rest of the document outlines various methods of drug discovery like serendipity, screening and molecular design. It also discusses processes like target selection, lead discovery, medicinal chemistry, in vitro and in vivo studies, and clinical trials.
The document discusses the importance of biotechnology in drug discovery. It notes that biotechnology has produced over 200 new therapies targeting various diseases. Biotechnology companies are more entrepreneurial and nimble compared to traditional pharmaceutical companies. The document also provides details on the large and growing biotech market in India and worldwide. It describes several applications of biotechnology across various stages of the drug discovery process, including target identification and validation, assay development, high-throughput screening, biomarker analysis, and protein engineering.
4th International Conference on Biomarkers & Clinical Research, will be organized around the theme "Impact of Biomarker Developments in Health Diagnostics and Clinical Research."
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptxDharaMehta45
The document provides an overview of the principles of drug discovery and development. It discusses the various phases including target identification and validation, hit identification and validation, lead selection and profiling, and pre-clinical and clinical development. The target identification process involves techniques like molecular biology, genetics, and data mining to identify potential biological targets. High-throughput screening is used to test large libraries of compounds to identify initial hits which are then optimized into drug candidates or leads through techniques such as medicinal chemistry and structure-activity relationships. The overall process takes 13-15 years and over $2 billion from initial drug discovery to regulatory approval and market launch.
WE THE STUDENT OF PHARMACEUTICAL CHEMISTRY FROM GURUNANAK COLLEGE OF PHARMACY HAS PRESENTED QSRR, TO MAKE READERS EASILY AVAILABLE, A COMPLETE TOPIC OF MPHARM 1ST YEAR WHICH WILL MAKE THEIR STUDY AND TO COLLECT DATA MORE EASILY AT A PLACE.
Provide statistical and computational tools for biologically based activities such as genetic analysis, measurement of gene expression, and gene function determination. Develop software or applications for scientific or technical use.
1. Unit I - new drug discovery and development.Audumbar Mali
The document summarizes the stages of drug discovery and development. It begins with drug discovery, which involves understanding disease pathways and identifying drug targets. Lead compounds are then identified and optimized. Preclinical testing assesses safety. If successful, an investigational new drug application is filed and clinical trials proceed in four phases, from initial safety testing to large efficacy trials. If approved, post-marketing monitoring continues to assess long-term safety. The process aims to bring safe and effective therapies to patients while adhering to regulatory standards.
INTRODUCTION
A PERFECT THERAPEUTIC DRUG
DRUG DISCOVERY- HISTORY
MODERN DRUG DISCOVERY
BIOINFORATICS IN DRUG DISCOVERY
DRUG DISCOVERY BASED ON BIOINFORMATIC TOOLS
BIOINFORMATICS IN COMPUTER-AIDED DRUG DISCOVERY
ECONOMICS OF DRUG DISCOVERY
CONCLUSION
REFERENCES
Research Avenues in Drug discovery of natural productsDevakumar Jain
This document discusses challenges facing the pharmaceutical industry and opportunities for natural products in drug discovery. The pharmaceutical industry faces losses of patent protection for many drugs, increasing costs, and litigation. Natural products are attractive alternatives as they have evolved to be bioactive and have structures not limited by human design. Advances like high-throughput screening, metabolomics, metagenomics, and metabolic engineering can help access natural product diversity and accelerate drug discovery from natural sources.
This document provides an overview of metabolomics and its applications in target identification. It discusses how metabolomics can be used to profile metabolites in biological samples and identify metabolic pathways and potential drug targets that are affected by diseases or drug treatments. It also describes how bioinformatics tools can integrate metabolomics data with other omics data to aid in target identification. The key steps involved are sample preparation, metabolite identification, metabolic pathway analysis, and computational analysis to predict potential drug targets within affected pathways.
The document discusses the role of genomics in pharmacogenomics and drug development. It defines key terms like pharmacogenomics and pharmacogenetics. It explains how genomics technologies can help optimize drug efficacy and minimize toxicity by identifying genetic variations that influence individual drug responses. Genomic information from the human genome project can aid drug target identification and reduce bottlenecks in development. Single nucleotide polymorphisms are discussed as the most common genetic variations affecting drug metabolism. The applications of pharmacogenomics in precision medicine to improve drug safety and efficacy are summarized.
What is biomarker?
What is the purpose of biomarker
Processes of biomarker development?
Types of Biomarkers
What is biomarker testing for cancer treatment?
Uses of Biomarkers in Cancer Medicine
Uses of Biomarkers in Cancer Drug Discovery
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Osteoporosis - Definition , Evaluation and Management .pdf
Drug discovery and development
1.
2. Introduction
• In the past most drugs have been discovered either by
identifying the active ingredient from traditional
remedies or by serendipitous discovery.
• But now we know diseases are controlled at molecular
and physiological level.
• Also shape of an molecule at atomic level is well
understood.
• Information of Human Genome
3. History of Drug Discovery :
Pre 1919
• Herbal Drugs
• Serendiptious discoveries
1920s, 30s
• Vitamins
• Vaccines
1940s
• Antibiotic Era
• R&D Boost due to WW2
1950s
• New technology,
• Discovery of DNA
1960s
• Breakthrough in Etiology
1970s
• Rise of Biotechnology
• Use of IT
1980s
• Commercialization of
Drug Discovery
• Combinatorial Chemistry
1990s
• Robotics
• Automation
4. Registration:
• The Ministry of health & Family Welfare and the
Ministry of Chemicals & Fertilizers have major role in
regulation of IPM.
• NDA must be submitted to DCGI
• Phase III study reported to CDL, Kolkata
• Package inserted approved by DCI
• Marketing approval from FDA
5. • ~$800 M spent to bring a new drug to
market.
• $127 Billion spent on Pharma R&D in
2010
• Share of CROs in research operations
is 27%
• World CRO market is 16.3 B (Indian
share $500 M)
Market Scenerio:
18.8
R&D Share
6. Top CROs (By Revenue)
Contract Research Organizations Revenue
Quintiles $2.5 Billion
Pharmaceutical Product Development $1.8 Billion
Covance $1.4 Billion
Charles River Laboratories $1.2 Billion
Parexel $930 Million
Icon $887 Million
Kendle $590 Million
Pharmanet $470 Million
PRA International $410 Million
4G Pharmacovigilance $391 Million
7. Top CROs (India)
Contract Research Organizations Location
Actimus Biosciences Hyderabad
Advinus Therapeutics Bangalore
Aurigene Discovery technologies Bangalore
Chembiotek Kolkata
GVK Biosciences Hyderabad
Jubilant Organosys Bangalore
Ranbaxy Life Sciences Mumbai
Reliance Life Sciences Mumbai
Suven Life Sciences Hyderabad
Syngene Bangalore
8. Most valuable R&D Projects
Rank Product Company Phase Pharmacological class
Today's
NPV($mn)
1 Degludec Novo Nordisk Phase III Insulin 5,807
2 Tofacitinib Pfizer Phase III JAK-3 inhibitor 4,953
3 BG-12 Biogen Idec Phase III Fumarate 4,666
4 Incivek J & J Phase IV Hep C protease inhibitor 4,332
5 Relovair Theravance Phase III Corticosteroid 4,241
6 DR Cysteamine Undisclosed Phase III
Lysosomal transport
modulator
4,155
7 AMR 101 Undisclosed Phase III Omega-3 fatty acid 4,052
8 Eliquis Bristol Myers Squibb Phase IV Factor Xa inhibitor 3,836
9 Eliquis Pfizer Phase IV Factor Xa inhibitor 3,592
10 Bexssero Novartis Phase IV Meningococcal B vaccine 3,250
9. Top Companies by R&D Expense:
Sr. No. Company R & D spend($bn),2010
1 Novartis 7.9
2 Merck & Co 8.1
3 Roche 7.8
4 GlaxoSmithKline 5.7
5 Sanofi 5.8
6 Pfizer 9.1
7 Johnson & Johnson 4.5
8 Eli Lilly 4.7
9 AstraZeneca 4.2
10 Takeda 3.4
11 Bayer 2.3
12 Bristol-Myers Squibb 3.3
13 Boehringer Ingelheim 3.1
14 Amgen 2.8
15 Novo Nordisk 1.7
10. Drug Development Cost Break-up
R&D Function %
Discovery/Basic Research
Synthesis & Extraction 10.0
Biological Screening & testing 14.2
Preclinical Testing
Toxicology & Safety testing 4.5
Pharmaceutical Dosage Formulation 7.3
Clinical Trials
Phase I, II, III 29.1
Phase IV 11.7
Manufacturing & QC 8.3
IND & NDA 4.1
Bioavailability 1.8
Others 9.0
Total 100.0
11. 10,000
COMPOUNDS
250
COMPOUNDS 5 COMPOUNDS
1 FDA
APPROVED
DRUG
~6.5 YEARS ~7 YEARS ~1.5 YEARS
DRUG
DISCOVERY
PRECLINICAL
CLINICAL TRIALS FDA
REVIEW
Drug Discovery &
Development-Timeline
12. Drug Discovery
• Drugs Discovery methods:
– Random Screening
– Molecular Manipulation
– Molecular Designing
– Drug Metabolites
– Serendipity
13. Target
Selection
• Cellular and
Genetic
Targets
• Genomics
• Proteomics
• Bioinformatics
Lead
Discovery
• Synthesis and
Isolation
• Combinatorial
Chemistry
• Assay
development
• High-
Throughput
Screening
Medicinal
Chemistry
• Library
Development
• SAR Studies
• In Silico
Screening
• Chemical
Synthesis
In Vitro
Studies
• Drug Affinity
and
Selectivity
• Cell Disease
Models
• MOA
• Lead
Candidate
Refinement
In Vivo
Studies
• Animal
models of
Disease States
• Behavioural
Studies
• Functional
Imaging
• Ex-Vivo
Studies
Clinical
Trials and
Therapeutics
14. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Target Selection
• Target selection in drug discovery is defined as the
decision to focus on finding an agent with a particular
biological action that is anticipated to have therapeutic
utility — is influenced by a complex balance of scientific,
medical and strategic considerations.
• Target identification: to identify molecular targets that
are involved in disease progression.
• Target validation: to prove that manipulating the
molecular target can provide therapeutic benefit for
patients.
15. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Target Selection
Biochemical Classes of Drug Targets
G-protein coupled receptors - 45%
enzymes - 28%
hormones and factors - 11%
ion channels - 5%
nuclear receptors - 2%
Techniques for Target Identification
16. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Cellular & Genetic Targets:
Involves the identification of the function of a potential therapeutic drug
target and its role in the disease process.
For small-molecule drugs, this step in the process involves identification
of the target receptors or enzymes whereas for some biologic
approaches the focus is at the gene or transcription level.
Drugs usually act on either cellular or genetic chemicals in the body,
known as targets, which are believed to be associated with disease.
17. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Cellular & Genetic Targets:
Scientists use a variety of techniques to identify and
isolate individual targets to learn more about their
functions and how they influence disease.
Compounds are then identified that have various
interactions with the drug targets that might be
helpful in treatment of a specific disease.
18. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Genomics:
The study of genes and their function. Genomics aims to
understand the structure of the genome, including the mapping
genes and sequencing the DNA.
Seeks to exploit the findings from the sequencing of the human
and other genomes to find new drug targets.
Human Genome consists of a sequence of around 3 billion
nucleotides (the A C G T bases) which in turn probably encode
35,000 – 50,000 genes.
19. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Genomics:
Drew’s estimates that the number of genes implicated in disease,
both those due to defects in single genes and those arising from
combinations of genes, is about 1,000
Based on 5 or 10 linked proteins per gene, he proposes that the
number of potential drug targets may lie between 5,000 and
10,000.
Single Nucleotide Polymorphism (SNP) libraries: are used to
compare the genomes from both healthy and sick people and to
identify where their genomes vary.
20. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Proteomics:
It is the study of the proteome, the complete set of proteins
produced by a species, using the technologies of large – scale protein
separation and identification.
It is becoming increasingly evident that the complexity of biological
systems lies at the level of the proteins, and that genomics alone will
not suffice to understand these systems.
It is also at the protein level that disease processes become manifest,
and at which most (91%) drugs act.
Therefore, the analysis of proteins (including protein-protein, protein-
nucleic acid, and protein ligand interactions) will be utmost importance
to target discovery.
21. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Proteomics:
Proteomics is the systematic high-throughput separation
and characterization of proteins within biological systems.
Target identification with proteomics is performed by
comparing the protein expression levels in normal and
diseased tissues.
2D PAGE is used to separate the proteins, which are
subsequently identified and fully characterized with LC-
MS/MS.
22. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Bioinformatics:
Bioinformatics is a branch of molecular biology that involves extensive analysis of
biological data using computers, for the purpose of enhancing biological research.
It plays a key role in various stages of the drug discovery process including
target identification
computer screening of chemical compounds and
pharmacogenomics
23. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Cellular &
Genetic Targets
Genomics
Proteomics
Bioinformatics
Bioinformatics:
Bioinformatics methods are used to transform the raw sequence
into meaningful information (eg. genes and their encoded
proteins) and to compare whole genomes (disease vs. not).
Can compare the entire genome of pathogenic and non-
pathogenic strains of a microbe and identify genes/proteins
associated with pathogenism
Using gene expression micro arrays and gene chip technologies, a
single device can be used to evaluate and compare the
expression of up to 20000 genes of healthy and diseased
individuals at once
24. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Synthesis and
Isolation
Combinatorial
Chemistry
Assay
Development
High
Throughput
Screening
Lead Discovery:
• Identification of small molecule modulators of
protein function
• The process of transforming these into high-
content lead series.
25. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Synthesis and
Isolation
Combinatorial
Chemistry
Assay
Development
High
Throughput
Screening
Synthesis and Isolation:
• Separation of mixture
• Separation of impurities
• In vitro chemical synthesis
• Biosynthetic intermediate
26. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Synthesis and
Isolation
Combinatorial
Chemistry
Assay
Development
High
Throughput
Screening
Combinatorial Chemistry:
Rapid synthesis of or computer simulation of
large no. of different but structurally related
molecules
• Search new leads
• Optimization of target affinity & selectivity.
• ADME properties
• Reduce toxicity and eliminate side effects
27. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Synthesis and
Isolation
Combinatorial
Chemistry
Assay
Development
High
Throughput
Screening
Assay Development
• Used for measuring the activity of a drug.
• Discriminate between compounds.
• Evaluate:
• Expressed protein targets.
• Enzyme/ substrate interactions.
28. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Synthesis and
Isolation
Combinatorial
Chemistry
Assay
Development
High
Throughput
Screening
High throughput screening:
• Screening of drug target against selection of
chemicals.
• Identification of highly target specific
compounds.
29. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Synthesis and
Isolation
Combinatorial
Chemistry
Assay
Development
High
Throughput
Screening
High throughput screening:
30. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Library
Development
SAR Studies
In Silico
Screening
Chemical
Synthesis
Medicinal Chemistry:
• It’s a discipline at the intersection of synthetic
organic chemistry and parmacology.
• Focuses on small organic molecules (and not
on biologics and inorganic compounds)
• Used in
• Drug discovery (hits)
• Lead optimization (hit to lead)
• Process chemistry and development
31. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Library
Development
SAR Studies
In Silico
Screening
Chemical
Synthesis
Library Development:
• Collection of stored chemicals along with
associated database.
• Assists in High Throughput Screening
• Helps in screening of drug target (hit)
• Based on organic chemistry
32. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Library
Development
SAR Studies
In Silico
Screening
Chemical
Synthesis
SAR Studies:
• Helps identify pharmacophore
• The pharmacophore is the precise section of
the molecule that is responsible for biological
activity
• Enables to prepare more active compound
• Allow elimination of excessive functionality
34. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Library
Development
SAR Studies
In Silico
Screening
Chemical
Synthesis
In silico screening:
• Computer simulated screening of chemicals
• Helps in finding structures that are most likely
to bind to drug target.
• Filter enormous Chemical space
• Economic than HTS
35. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Library
Development
SAR Studies
In Silico
Screening
Chemical
Synthesis
Chemical Synthesis:
• Involve production of lead compound in
suitable quantity and quality to allow large
scale animal and eventual, extensive human
clinical trials
• Optimization of chemical route for bulk
industrial production.
• Suitable drug formulation
36. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Drug Affinity
and Selectivity
Cell Disease
Models
MOA
Lead Candidate
Refinement
In Vitro Studies:
• (In glass) studies using component of organism i.e. test tube
experiments
• Examples-
• Cells derived from multicellular organisms
• Subcellular components (Ribosomes, mitochondria)
• Cellular/ subcellular extracts (wheat germ, reticulocyte
extract)
• Purified molecules (DNA,RNA)
37. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Drug Affinity
and Selectivity
Cell Disease
Models
MOA
Lead Candidate
Refinement
In Vitro Studies:
Advantages:
• Studies can be completed in short period of time.
• Reduces risk in post clinical trials
• permits an enormous level of simplification of the system
• investigator can focus on a small number of components
38. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Drug Affinity
and Selectivity
Cell Disease
Models
MOA
Lead Candidate
Refinement
Drug affinity and selectivity
• Drug affinity is the ability of drug to bind to its biological
target (receptor, enzyme, transport system, etc.)
• Selectivity- Drug should bind to specific receptor site on the
cell (eg. Aspirin)
39. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Drug Affinity
and Selectivity
Cell Disease
Models
MOA
Lead Candidate
Refinement
• Isogenic human disease models- are a family of cells that are
selected or engineered to accurately model the genetics of a specific
patient population, in vitro
• Stem cell disease models-Adult or embryonic stem cells carrying
or induced to carry defective genes can be investigated in vitro to
understand latent molecular mechanisms and disease characteristics
Cell disease models
40. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Drug Affinity
and Selectivity
Cell Disease
Models
MOA
Lead Candidate
Refinement
• Optimizing chemical hits for clinical trial is commonly referred
to as lead optimization
• The refinement in structure is necessary in order to improve
• Potency
• Oral Availability
• Selectivity
• pharmacokinetic properties
• safety (ADME properties)
Lead Candidate refinement
41. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Animal models of
Disease States
Behavioural
Studies
Functional
Imaging
Ex-Vivo Studies
In vivo studies
• Its experimentation using a whole, living
organism.
• Gives information about,
• Metabolic profile
• Toxicology
• Drug interaction
42. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Animal models of
Disease States
Behavioural
Studies
Functional
Imaging
Ex-Vivo Studies
Animal models of disease states
• Test conditions involving induced disease or
injury similar to human conditions.
• Must be equivalent in mechanism of cause.
• Can predict human toxicity in 71% of the
cases.
• Eg. SCID mice-HIV
NOD mice- Diabetes
Danio rerio- Gene function
43. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Animal models of
Disease States
Behavioural
Studies
Functional
Imaging
Ex-Vivo Studies
Behavioural Studies
• Tools to investigate behavioural results of drugs.
• Used to observe depression and mental disorders.
• However self esteem and suicidality are hard to induce.
• Example:
• Despair based- Forced swimming/ Tail suspension
• Reward based
• Anxiety Based
44. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Animal models of
Disease States
Behavioural
Studies
Functional
Imaging
Ex-Vivo Studies
Functional Imaging:
• Method of detecting or measuring changes in
metabolism, blood flow, regional chemical
composition, and absorption.
• Tracers or probes used.
• Modalities Used-
• MRI
• CT-Scan
45. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Animal models of
Disease States
Behavioural
Studies
Functional
Imaging
Ex-Vivo Studies
Ex-Vivo Studies:
• Experimentation on tissue in an artificial
environment outside the organism with the
minimum alteration of natural conditions.
• Counters ethical issues.
• Examples:
• Measurement of tissue properties
• Realistic models for surgery
46. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Clinical trials:
• Set of procedures in medical research and
drug development to study the safety and
efficacy of new drug.
• Essential to get marketing approval from
regulatory authorities.
• May require upto 7 years.
47. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Phase 0:
• Recent designation, also known as human micro-dosing
studies.
• First in human trials, conducted to study exploratory
investigational new drug.
• Designed to to speed up the development of promising
drugs.
• Concerned with-
• Preliminary data on the drug’s pharmacodynamics
and pharmacokinetics
• Efficacy of pre-clinical studies.
48. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Phase I:
• Clinical Pharmacologic Evaluation
• First stage of testing in human subjects.
• 20-50 Healthy Volunteers
• Concerned With:
– Human Toxicity.
– Tolerated Dosage Range
– Pharma-cology/dynamics
49. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Phase I:
Types of Phase-I Trials
• SAD (Single Ascending Dose)
• MAD (Multiple Ascending Dose)
• Food effect
50. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Phase II:
• Controlled Clinical Evaluation.
• 50-300 Patients
• Controlled Single Blind Technique
• Concerned With:
– Safety
– Efficacy
– Drug Toxicity
– Drug Interaction
51. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Phase III:
• Extended Clinical Trials.
• Most expensive & time consuming.
• 250-1000 Patients.
• Controlled Double Blind Technique.
• Concerned With:
– Safety, Efficacy
– Comparison with other Drugs
– Package Insert
52. Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-I
Phase-II
Phase-III
Phase-IV
Phase IV:
• Post Marketing Surveillance.
• Designed to detect any rare or long-term
adverse effects.
• Adverse Drug Reaction Monitoring.
• Pharmacovigilance.
53. 10,000
COMPOUNDS
250
COMPOUNDS 5 COMPOUNDS
1 FDA
APPROVED
DRUG
~6.5 YEARS ~7 YEARS ~1.5 YEARS
DRUG
DISCOVERY
PRECLINICAL
CLINICAL TRIALS FDA
REVIEW
Drug Discovery &
Development-Timeline
54. Gene Therapy
• Technique for correcting
defective genes.
• It is the process of inserting
genes into cells to treat
diseases.
• Gene therapy is used to
correct a deficient phenotype.
55. Gene Therapy-Approaches
Germline Gene Therapy
Sperm or eggs, are modified by the introduction of functional genes, which
are integrated into their genomes.
Change would be heritable and would be passed on to later generations.
Somatic Gene Therapy
The therapeutic genes are transferred
Into the somatic cells of a patient.
Change will not be inherited by the
patient's offspring or later generations.
56. Gene Therapy- Types
Ex Vivo Gene Therapy
Transfer of therapeutic genes in cultured cells which are then reintroduced
into patient.
Eg: Therapy for ADA Deficiency
In Vivo Gene Therapy
The direct delivery of genes into the cells of a particular tissue is referred
to as in vivo gene therapy.
Eg: Therapy for Cystic fibrosis
57. Gene Therapy- Vectors
• Viruses
Retroviruses
Adenoviruses
Adeno-associated viruses
Herpes Simplex viruses
• Pure DNA Constructs
• Lipoplexes
• DNA Molecular Conjugates
• Human Artificial Chromosome
58. Gene Therapy- Limitations
• Short lived nature of gene therapy
• Immune response
• Problems with viral vectors
• Multigene disorders
59. Recent Developments
• Nanotechnology + gene therapy yielded treatment to
torpedo cancer
• Results of world's first gene therapy for inherited
blindness show sight improvement
• New Method of Gene Therapy Alters Immune Cells for
Treatment of Advanced Melanoma
• Dual Gene Therapy Suppresses Lung Cancer in
Preclinical Test
60. Orphan Drugs:
• An orphan drug is a pharmaceutical agent that has been
developed specifically to treat a rare medical condition,
the condition itself being referred to as an orphan disease.
• National Organization for Rare
Disorders
• European Organization for Rare
Diseases
61. Advantages:
• Tax incentives.
• Enhanced patent protection and marketing rights.
• Clinical research financial subsidization.
• Rise in research and developmen.
• Crown Corporation.
62. Orphan Drugs Act:
• 4th January 1983
• 6000 Orphan Diseases
• Unprofitable Drug Development
• Affecting < 2,00,000 Persons
• Orphan Drug Status to 1,090
Drugs
• 1985 Amendment- Marketing
Exclusivity
Tourette Syndrome
An Orphan Disease
63. FDA Orphan Drug Approvals:
43
19
17
19
2
% Share
Big Pharma
Small Biopharma
Established
Biopharma
Small & Medium
Pharma