Drug Targets

Question 1

4 stages of Drug Life Cycle

Answer 1

Research & Discovery, Non-Clinical, Clinical and Post Approval. 1st 2 = study based. last 2 = process (/manufacturing) based

Question 2

3 Stages on In-Vitro and In-Vivo Testing

Answer 2

Basic Research, Early Discovery and Pre Clinical

Question 3

Human Testing

Answer 3

3 phases of clinical trials

Question 4

Early Drug Discovery Steps

Answer 4

Target ID & Validation, Hit Discovery, Assay Dev & Screening, HTS, Hit to Lead and Lead Optimization

Question 5

Pre-Clinical Study Steps

Answer 5

ADME, Proof Concept, Drug Delivery, formulation optimisation & bioavailability, dose range, safety + efficacy, pharmacokinetic analysis and bioanalytical method

Question 6

Clinical Development

Answer 6

Phase 1 (Healthy Volunteer Study, safety + efficacy), Phase 2 (patient pop study), Phase 3 (dose escalation). Pharmacokinetic analysos, bioanalytical method dev

Question 7

Relationship between number of drugs on market and cost of drug developing

Answer 7

More drugs on market = more expensive to put drugs on market

Question 8

How Many Drugs Fail Clinical Trials

Answer 8

90%

Question 9

Stages in Drugs Discovery

Answer 9

Disease ID, Target ID (all possible targets), Target Validation (eliminate wrong targets), HTS, Seed ID, Primary Screening Assay, Lead ID, Lead Optimisation and Animal Model

Question 10

Disease Identification Considerations

Answer 10

Disease pathophysiology + symptoms, disease definition, patient population, pre-existing therapies (+ where they fall short), competitors

Question 11

Health Def

Answer 11

State of complete physical, mental and social well being

Question 12

Disease Def

Answer 12

Abnormal condition that impairs body function with specific signs and symptoms. What is abnormal changes with age and culture

Question 13

Creating A Disease

Answer 13

Occasionally diseases are defined by a company when they need clearance for their drug (know physiological effects, before they know if it treats anything). Is it a collection of diseases (eg cancer)

Question 14

Market Research

Answer 14

Important to know if profit can be made from drug (main motivation in industry)

Question 15

Benefits in Orphan Drug

Answer 15

(<0.05% people experience) Tax incentives, reduced regulatory requiremnts

Question 16

Existing Therapies Considerations

Answer 16

Drug efficiency, adverse effects, target action, accessibility, patents, competitor resources

Question 17

Drug Target Outline

Answer 17

Molecular entity that drugs bind to, to mediate effects. Usually enzymes or cell receptors

Question 18

Target ID Outline

Answer 18

Necessary to predict drug action and efficacy. Proteins identified in novel target ID in disease. Aids approval process for animal trials (better understanding of MOA)

Question 19

Target ID Advantages

Answer 19

Allows HTS, allows functional screens, allows molecular modelling use, allows toxic target elimination and aids approval process

Question 20

How are novel targets identified

Answer 20

Researching disease processes

Question 21

How to contrast novel vs diseased tissue

Answer 21

Altered levels of protein (gene expression)

Question 22

Analysis of Diseased Tissues

Answer 22

SNP analysis, Polymorphism comparison, gene expression comparison, genomics, protein expression comparison and proteomics

Question 23

Comparison Problem

Answer 23

Precise disease definition, patient recruitment, ‘normal’ volunteer recruitment (and possibly only early stage), multiple disease causes

Question 24

Genomic Studies

Answer 24

mRNA extracted, cDNA generated, cDNA labled, array of genes probed and data analysed

Question 25

Microarray Analysis Problems

Answer 25

Overly simplistic, natural variation in gene expression and number of genes needing to be processed

Question 26

Proteomics Outline

Answer 26

Study of protein's in a tissue. Doesn't use mRNA (less stability coniderations), more protein then genes (splice variations, more possible targets)

Question 27

Problems With 2D gel Electrophoresis

Answer 27

Many different gels necessary, specialised software necessary, differnet to quantitate differences

Question 28

Protein Arrays

Answer 28

Alternative to genes. Used to identify antibodies. Identify protein-protein interactions

Question 29

Bioinformatics Outline

Answer 29

Handling of data fom proteomic and genomic experiments. Broad including hardware, analysis and modelling

Question 30

Target Validation

Answer 30

Obtain evidence of drugs acting on specific targets modifying disease. Use of antibodies, polymorphisms in disease