Overview Of Preclinical Research

Question 1

Define preclinical research

Answer 1

Research that is conducted before clinical trials

Question 2

Drug target

Answer 2

A target that a molecule binds to produce a desirable effect

Question 3

Pathway analysis

Answer 3

Network of proteins associated with a particular disease

Question 4

Phenotype studies

Answer 4

Studying the morphology, migration and invasion capacity of cells (disease cells generally move faster from one place to another and invade surrounding tissue)

Question 5

To find new drug targets what happens?

Answer 5

Compare gene/protein expression between normal vs disease
Pathway analysis
Phenotype studies

Question 6

Companies tend to concentrate on developing drugs for diseases that are prevalent in developed nations, why?

Answer 6

Strong focus on diseases like cancer, flu, depression
Developing countries don’t have resources or funding in place

Question 7

Why is malaria an exception? For developing drugs in developed nations?

Answer 7

Due to tourism and spread of malaria to southern States of US

Question 8

Screening libraries

Answer 8

Compound libraries
Need to find a hit’ candidate drug
High through put and less resource intensive than phenotypic approach

Question 9

High throughput screening

Answer 9

Large number of compounds are tested very quickly in anautomated fashion

Question 10

Lead optimisation is when?

Answer 10

Medicinal chemists make changes to chemical groups of compounds to make it more selective, potent, effective etc

Question 11

Primary screen

Answer 11

High through put screening of hundred of thousands of compounds to identity active compounds against target

Question 12

Compound screening cascade

Answer 12

Primary screen
Secondary screen
Lead optimasition - medicinal chemists make changes to chemical groups ofcompounds to make it more selective, potent, elective etc
Safety and toxicity
Efficacy
Clinical trials-only one

Question 13

Target selection and validation

Answer 13

Primary screen, secondary screen, leads optimisation, safety and toxicity, efficacy

Question 14

In vitro

Answer 14

Experiments outside an organism in test tubes

Question 15

Advantages, of in vitro

Answer 15

High throughput screening
Reduced costs
Less regulations

Question 16

In vivo

Answer 16

Experiments inside an intact living organism

Question 17

Disadvantages in vivo

Answer 17

Highly regulated
Low throughput
Not able to model all aspects of human diseases
Long term models relatively short term
Species differences in biology
Animal studies have limited genetic diversity
Carried out under controlled environments

Question 18

Ex vivo

Answer 18

Experiments of intact tissue/organs outside a living organism

Question 19

In silico

Answer 19

Experiments using computer simulation

Question 20

Cell line is a permanently established?

Answer 20

Cell culture that will proliferate indefinitely given appropriate fresh medium and space. They are immortalised

Question 21

Importance of cell line

Answer 21

Important for studying physiology, pathology and cell growth
Tell us about alterations in structure, function and grout makeup of the cell under controlled environments

Question 22

Cell line limitations

Answer 22

Not reflective of the biology of living organisms

Question 23

How is cell line established?

Answer 23

Cells extracted from humans or animals
Introduction of an aberration with the appropriate space and cellmedium

Question 24

Aberration

Answer 24

An abnormality of the chromosome number in a cell

Question 25

Lead optimisation is a process by which?

Answer 25

A drug candidate is further improved after an initial lead compounds is identified

Question 26

Lead optimisation aims at enhancing the mostpromising compounds how?

Answer 26

Improve effectiveness
Reduce toxicity
Increase absorption

Question 27

Why does drug development fail?

Answer 27

Don’t work-efficacy
Not safe -toxicity

Question 28

Lead optimisation: lipinski rule of 5

Answer 28

Molecular weight <500
Solubility log p<5
< 10 hydrogen bond acceptors
<5 hydrogen bond donors

Question 29

Therapeutic index is a measure of?

Answer 29

Drug safety

Question 30

Higher therapeutic index

Answer 30

Bigger window of drug effect

Question 31

5 Rs

Answer 31

Right target
Right tissue
Right safety
Right patient
Right commercial - defining the right commercial value and future viability

Question 32

Absorption

Answer 32

Movement of drug from its side of administration into the blood

Question 33

Distribution

Answer 33

Movement of drugs throughout the body

Question 34

Metabolism

Answer 34

Transformation of pharmaceutical substances into metabolites

Question 35

Excretion

Answer 35

Removal of pharmaceutical substances from the body

Question 36

Target occupancy

Answer 36

Measures the degree to which the test drug occupies its target in the tissue/animal

Question 37

Toxicology testing is required to?

Answer 37

Demonstrate that drugs are safe before they can be given to humans

Question 38

In vitro toxicology provides an early indication of?

Answer 38

The potential for some kind of toxic effects, allowing a decision to terminate a development program before spending too much money

Question 39

Characteristics of in vitro toxicology

Answer 39

Less expensive to ran than in vivo
Faster than in vivo

Question 40

Modelling in vitro toxicology study:

Answer 40

Drug in interest and control added to cells
then add SYTOX to drug Petri dish ( if cells die, then cells turn green)- if killing normal cells, then the drug is toxic

Question 41

High throughput screening

Answer 41

Is a drug discovery process that allows automated testing of large numbers of chemical and/or biological compounds for a specitio biological target.
They accurate target analysis, as large scale compound libraries canquickly be screened in a cost effective way

Question 42

What information does “target occupancy” show in the development of a drug?

Answer 42

It shows evidence that the target site is occupied by the drug candidate to the intended extent