Podcast
Questions and Answers
What is the estimated cost of bringing a drug to market, including both successful and unsuccessful programs?
What is the estimated cost of bringing a drug to market, including both successful and unsuccessful programs?
What is the primary goal of the target identification stage in drug discovery?
What is the primary goal of the target identification stage in drug discovery?
Which of the following is NOT a major technology used for target identification in drug discovery?
Which of the following is NOT a major technology used for target identification in drug discovery?
During which stage is it confirmed that a biological target is directly involved in a disease process?
During which stage is it confirmed that a biological target is directly involved in a disease process?
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Which type of omics technology focuses on the study of small molecules within an organism?
Which type of omics technology focuses on the study of small molecules within an organism?
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What proportion of drugs that enter clinical trials is estimated to receive approval?
What proportion of drugs that enter clinical trials is estimated to receive approval?
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What is the primary purpose of target identification in drug discovery?
What is the primary purpose of target identification in drug discovery?
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Which manufacturing process is associated with biologics compared to small molecule drugs?
Which manufacturing process is associated with biologics compared to small molecule drugs?
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Which of the following cannot be considered part of the druggable genome?
Which of the following cannot be considered part of the druggable genome?
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What is the main aim of target validation in drug discovery?
What is the main aim of target validation in drug discovery?
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Which method is NOT typically used in hit identification?
Which method is NOT typically used in hit identification?
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Which characteristic best differentiates small molecule drugs from biologics?
Which characteristic best differentiates small molecule drugs from biologics?
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Which characteristic is essential for a valid drug target ensuring its modulation leads to a therapeutic effect?
Which characteristic is essential for a valid drug target ensuring its modulation leads to a therapeutic effect?
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What is a significant advantage of Antibody-Drug Conjugates (ADCs) in cancer therapy?
What is a significant advantage of Antibody-Drug Conjugates (ADCs) in cancer therapy?
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What does the term 'hit identification' in drug discovery processes refer to?
What does the term 'hit identification' in drug discovery processes refer to?
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What is the primary purpose of ADMET studies in drug optimization?
What is the primary purpose of ADMET studies in drug optimization?
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Which process is used to refine hits from screening methods into lead compounds?
Which process is used to refine hits from screening methods into lead compounds?
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Which component of Antibody-Drug Conjugates (ADCs) is responsible for targeting specific antigens on cancer cells?
Which component of Antibody-Drug Conjugates (ADCs) is responsible for targeting specific antigens on cancer cells?
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What is the primary role of biomarkers in drug target validation?
What is the primary role of biomarkers in drug target validation?
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What key factor is assessed to determine whether a target can be effectively modulated by a drug?
What key factor is assessed to determine whether a target can be effectively modulated by a drug?
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What is the primary goal of Phase 1 clinical trials?
What is the primary goal of Phase 1 clinical trials?
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Which type of application is specifically designed for biologics such as vaccines?
Which type of application is specifically designed for biologics such as vaccines?
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What is a significant benefit of Phenotypic Drug Discovery (PDD) compared to Target-Based Drug Discovery (TDD)?
What is a significant benefit of Phenotypic Drug Discovery (PDD) compared to Target-Based Drug Discovery (TDD)?
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Cell Painting in Phenotypic Drug Discovery is primarily used to capture what type of data?
Cell Painting in Phenotypic Drug Discovery is primarily used to capture what type of data?
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What aspect of drug safety does post-marketing monitoring primarily focus on?
What aspect of drug safety does post-marketing monitoring primarily focus on?
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Which statement best describes the difference between High-Content Screening (HCS) and Cell Painting?
Which statement best describes the difference between High-Content Screening (HCS) and Cell Painting?
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During which phase of clinical trials do drugs face the highest risk of failure in terms of advancement to the next phase?
During which phase of clinical trials do drugs face the highest risk of failure in terms of advancement to the next phase?
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What type of change can be observed using transcriptomics in phenotypic drug screenings?
What type of change can be observed using transcriptomics in phenotypic drug screenings?
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What is one of the main advantages of using multiple fluorescent dyes in Cell Painting?
What is one of the main advantages of using multiple fluorescent dyes in Cell Painting?
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What is evaluated in Phase 2 clinical trials primarily?
What is evaluated in Phase 2 clinical trials primarily?
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Study Notes
Drug Discovery and Development Process
- Drug development takes 12-15 years to market approval.
- Only 1 in 10 drugs in clinical trials is approved.
- Cost to bring a drug to market is estimated at $2.6 billion.
- WHO defines a drug as a substance or product intended to change physiological or pathological states for benefit.
Drug Discovery
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Finding a compound with therapeutic benefits for treating diseases.
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Primary Stages
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Target Identification: Identifying suitable disease-related targets for drug development (efficient, safe, usable, clinically/commercially viable).
- Potential targets: proteins and nucleic acids.
- Technologies:
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Target Identification: Identifying suitable disease-related targets for drug development (efficient, safe, usable, clinically/commercially viable).
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Omics-Based Methods:
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Genomics: studies an organism's complete DNA.
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Transcriptomics: studies the complete set of RNA transcripts.
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Proteomics: large-scale study of proteins.
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Metabolomics: studies small molecules (metabolites) in cells and fluids.
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3D structure analysis: Example: cancer.
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Find disease proteins to inhibit.
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Screen molecules against these targets.
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Target Validation: Confirming a biological target's direct involvement in a disease process and the therapeutic benefit of modifying it.
- Target Criteria:
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Target Validation: Confirming a biological target's direct involvement in a disease process and the therapeutic benefit of modifying it.
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Effective: Critical to disease process and modulates it therapeutically.
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Safe: Modifying the target does not cause unacceptable side effects.
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Usable: Developing an effective drug to engage the target is feasible.
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Meeting Clinical and Commercial Requirements: including regulatory, IP, market, and commercial viability considerations.
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Hit Identification/Hit Finding: Identifying compounds potentially binding to a target and affecting its activity.
- Techniques:
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Hit Identification/Hit Finding: Identifying compounds potentially binding to a target and affecting its activity.
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High-throughput screening.
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Fragment-based drug discovery.
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Structure-based drug design.
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Virtual screening.
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De novo design.
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Hit-to-Lead and Lead Optimization: Improving hit compounds for preclinical testing.
- Optimization Process:
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Hit-to-Lead and Lead Optimization: Improving hit compounds for preclinical testing.
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Quantitative Structure-Activity Relationship (QSAR) and Structure-Function Relationship studies.
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ADMET studies (Absorption, Distribution, Metabolism, Excretion, Toxicity).
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Improving properties like potency, efficacy, selectivity, and bioavailability.
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Medicinal chemistry.
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Antibody-Drug Conjugates (ADCs).
Antibody-Drug Conjugates (ADCs)
- Combination of antibody specificity and cytotoxic drug potency for targeted cancer therapy.
- Structure:
- Monoclonal antibody targets cancer antigens.
- Cytotoxic drug (warhead) kills cancer cells.
- Linker connects antibody and drug.
- Mechanism of Action: antibody binds, ADC internalized, cytotoxic drug released, cancer cell destroyed.
- Advantages: targeted delivery, improved therapeutic index, enhanced specificity.
- Examples: Adcetris, Polivy, Padcev, Tivdak.
Preclinical Development (Stage 5)
- Manufacturing and testing lead compound efficiency and safety for regulatory submission.
- Pharmacodynamics (PD): Drug's biochemical and physiological effects; how it interacts with targets and impacts systems.
- Pharmacokinetics (PK): Drug movement in the body (ADME) important for optimal dosage, route, and frequency.
Clinical Development (Stage 6)
- Testing drugs on humans (4 phases).
- Phase 1: Safety and dosage (20-100 volunteers).
- Phase 2: Efficacy and side effects (several hundred volunteers).
- Phase 3: Further efficacy and adverse reaction monitoring (300-3,000 volunteers).
- Phase 4: Continued safety and efficacy monitoring after approval.
- Drug Application and FDA Approval: NDA, OTC, BLA applications.
- Post-marketing monitoring.
Early-Phase Drug Discovery Strategies
- **Target-Based Drug Discovery (TDD):** Uses known relationships between a target and disease.
- **Phenotypic Drug Discovery (PDD):** Observes compound effects without prior target knowledge.
Phenotypic Drug Discovery Benefits
- Unbiased approach: no prior target knowledge.
- Disease relevance: models closely mimic human disease.
- Reduced target validation failure risks.
- Identifies polypharmacology (drugs that target multiple pathways).
Phenotypes in PDD
- Cell metabolism changes (metabolomics).
- Protein activity changes (phosphoproteomics)
- Protein levels changes (proteomics).
- Gene expression changes (transcriptomics).
- Cell shape or structure changes (imaging).
Cell Painting in PDD
- High-content imaging technique to observe cellular changes after drug treatment.
- Multi-dye staining to visualize cell components.
- Image analysis to extract morphological profiles.
- Advantage: unbiased, comprehensive, high-dimensional data, novel target and mechanism identification.
- Compared to High Content Screening (HCS) , which is more focused on predefined phenotypes.
Small Molecule vs. Biological Drugs
- Small Molecule: -Small size, well-defined structure, relatively stable, synthesized by predictable chemical reactions, usually not immunogenic, relatively easy to characterize.
- Biological Drugs: -Large size, complex structure, sensitive to storage/handling, produced in living cells, can be immunogenic, require more characterization studies.
FDA Approved Drugs (1981-2019)
- Drug origin and production method data was provided in percentages.
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Description
Explore the intricate phases of drug discovery and development, from target identification to market approval. Learn about the challenges faced in clinical trials and the various omics-based methods used in the process. This quiz will provide insights into the timelines and costs associated with bringing a drug to market.
