Overview Of Preclinical Research Flashcards

(42 cards)

1
Q

Define preclinical research

A

Research that is conducted before clinical trials

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2
Q

Drug target

A

A target that a molecule binds to produce a desirable effect

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3
Q

Pathway analysis

A

Network of proteins associated with a particular disease

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4
Q

Phenotype studies

A

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

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5
Q

To find new drug targets what happens?

A

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

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6
Q

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

A

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

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7
Q

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

A

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

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8
Q

Screening libraries

A

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

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9
Q

High throughput screening

A

Large number of compounds are tested very quickly in anautomated fashion

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10
Q

Lead optimisation is when?

A

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

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11
Q

Primary screen

A

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

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12
Q

Compound screening cascade

A

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

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13
Q

Target selection and validation

A

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

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14
Q

In vitro

A

Experiments outside an organism in test tubes

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15
Q

Advantages, of in vitro

A

High throughput screening
Reduced costs
Less regulations

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16
Q

In vivo

A

Experiments inside an intact living organism

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17
Q

Disadvantages in vivo

A

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

18
Q

Ex vivo

A

Experiments of intact tissue/organs outside a living organism

19
Q

In silico

A

Experiments using computer simulation

20
Q

Cell line is a permanently established?

A

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

21
Q

Importance of cell line

A

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

22
Q

Cell line limitations

A

Not reflective of the biology of living organisms

23
Q

How is cell line established?

A

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

24
Q

Aberration

A

An abnormality of the chromosome number in a cell

25
Lead optimisation is a process by which?
A drug candidate is further improved after an initial lead compounds is identified
26
Lead optimisation aims at enhancing the mostpromising compounds how?
Improve effectiveness Reduce toxicity Increase absorption
27
Why does drug development fail?
Don't work-efficacy Not safe -toxicity
28
Lead optimisation: lipinski rule of 5
Molecular weight <500 Solubility log p<5 < 10 hydrogen bond acceptors <5 hydrogen bond donors
29
Therapeutic index is a measure of?
Drug safety
30
Higher therapeutic index
Bigger window of drug effect
31
5 Rs
Right target Right tissue Right safety Right patient Right commercial - defining the right commercial value and future viability
32
Absorption
Movement of drug from its side of administration into the blood
33
Distribution
Movement of drugs throughout the body
34
Metabolism
Transformation of pharmaceutical substances into metabolites
35
Excretion
Removal of pharmaceutical substances from the body
36
Target occupancy
Measures the degree to which the test drug occupies its target in the tissue/animal
37
Toxicology testing is required to?
Demonstrate that drugs are safe before they can be given to humans
38
In vitro toxicology provides an early indication of?
The potential for some kind of toxic effects, allowing a decision to terminate a development program before spending too much money
39
Characteristics of in vitro toxicology
Less expensive to ran than in vivo Faster than in vivo
40
Modelling in vitro toxicology study:
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
41
High throughput screening
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
42
What information does "target occupancy" show in the development of a drug?
It shows evidence that the target site is occupied by the drug candidate to the intended extent