Drug Discovery 1

Question 0

what substances are classed as drugs ?

Answer 0

biopolymers and vaccines

Question 1

define drug:

Answer 1

a single chemical substance that is conventionally marketed for use in medicine

Question 2

what is not classed as a drug ?

Answer 2

recreational drugs because they dont have therapeutic use
herbal remedies or dietary supplements because these are poorly defined and they dont undergo the regulatory procedures which medicinal drugs do
drug wannabees which are created during the drug development process because they are not marketed for

Question 3

what does drug discovery and development entail?

Answer 3

process of taking a therapeutic concept and converting it into a physical entity which is marketed for medicinal benefit and financial profit
it can take up to 15 years
its a mutli disciplinary challenge

Question 4

what are the examples of the different disciplines involved in producing a drug ?

Answer 4

computational synthetic and medicinal chemistry 
computational biology and bioinformatics 
molecular biology 
molecular pharmacology 
in vivo pharmacology 
clinical testing and evaluation 
safety pharmacologists 
marketing 
patent and regulatory law 
process chemistry and manufacturing

Question 5

what does NME stand for ?

Answer 5

new molecular entity

a new molecule which has been discovered to be used as a drug

Question 6

what is the challenge in drug discovery and development ?

Answer 6

same amount of cash is being spent but there are smaller amounts of drugs being produced
the cost:success ratio is increasing

Question 7

why is the cost:success ratio increasing?

Answer 7

because the easier drugs to develop have already been developed and because the regulations to produce drugs are much more stringent now

Question 8

what are the 6 stages in the developement of a new drug ?

Answer 8

1- discovery - about 1500
2- clinical trial 1- 9.1
3- clinical trial 2 - 5.5
4- clinical trial 3- 1.8 
5- regulation - 1.3 
6- launch - 1

Question 9

how many years does it take to discover a drug wannabee?

Answer 9

5 years

Question 10

how many years do pre-clinical trials take ?

Answer 10

1.5 years

Question 11

how many years does it take to do clinical trials?

Answer 11

6 years

Question 12

how many years does it take to do a FDA review?

Answer 12

2 years

Question 13

how many years does it take to manufacture the drug ?

Answer 13

2 years

Question 14

what are the reasons for high attrition rates ?

Answer 14

poor efficacy 
poor pharmacokinetics
toxicity in animal trials 
adverse effects in humans 
commerical reasons

Question 15

how have the attrition rates changed between 2000 and 2008?

Answer 15

in 2000 there were much higher rates of attrition due to poor pharmacokinetics, with 40% of drugs failing from this, however this has significantly reduced
however in 2008 the number of drugs failing due to commercial reasons has increased - more difficult and expensive to get drugs approved and there is fierce competition

Question 16

how are the attrition rates due to poor pharmacokinetics caused ?

Answer 16

poor effect of the body to the drug due to not getting the drug to the target and it has adverse effects elsewhere

Question 17

what is the main reason for a drug failing during the clinical trials ?

Answer 17

2/3s is due to insufficient efficacy

1/5 is due to safety issues

Question 18

what are the 4 main reasons to start/complete a drug discovery project ?

Answer 18

scientific reasons
development
strategic reasons
operational reasons

Question 19

what are the scientific reasons to start/complete a drug discovery project?

Answer 19

strength of hypothesis
target availability
assay availability 
animal models 
chemical starting point

Question 20

what are the development reasons to start/complete a drug discovery project?

Answer 20

competition 
patents 
toxicology 
clinical development 
production 
regulation

Question 21

what are the strategic reasons to start/complete a drug discovery project ?

Answer 21

market predictions
unmet medical need
company strategy
current drug pipeline

Question 22

what are the operational reasons to start/complete a drug discovery project?

Answer 22

resources
costs
staff expertise
company facilities

Question 23

what is “translational chemistry” ?

Answer 23

observation that a particular substance exhibits biological activity that may be of interest…. explore link between the chemical and the activity to improve these properties
main point= there was no idea about the disease/therapy at the start- there is potential for this drug to treat any disease

Question 24

what is “translational biology”?

Answer 24

observation of a biological property and concept that it could be manipulated for therapeutic benefit….. then the pursuit of a substance that can modulate this biology
main point= start with the biology instead of the compound - attempt to find a compound which will modulate a biological property

Question 25

what is an example of translational chemistry ?

Answer 25

discovery of d-turbocurarine
it was a plant extract used by south american natives to attach to their arrows to immobilise their prey when hunting
“concept”- can we understand the unusual properties of this plant
“drug discovery/development”- can this understanding be developed into real life

Question 26

what does d-tubocurarine?

Answer 26

it causes muscle paralysis

further development showed that it is a blocker of the nicotinic acetyl choline receptor at neuromuscular junctions

Question 27

what have d-tubocurarine analogues been used in ?

Answer 27

used in open chest surgery to paralyse the diaphragm