Drug discovery and drug design

Question 1

What is a drug?

Answer 1

A medicine or other substance that has a physiological effect when ingested or otherwise introduced into the body

Question 2

How long can it take to launch a new drug?

Answer 2

12-15 years

Question 3

How much money can it cost to make a new drug?

Answer 3

1 billion

Question 4

Why do drugs fail in the clinic?

Answer 4

• they dont work
• they arent safe

Question 5

what are the different stages of drug development?

Answer 5

• drug discovery
• pre clinical

Question 6

Pre clinical

Answer 6

target identification
target assay construction and screening
target validation

Question 7

How many phases are there for trails

Answer 7

4

Question 8

how is a target validated?

Answer 8

genetic, cellular and in vivo experuments
compound screening
secondary analysis
in vivo analysis

Question 9

Target identification techniwues

Answer 9

Data mining using available bioinformatics
genetic association studies
phenotypic screening to see biological effects

Question 10

Interaction validation

Answer 10

Study the interactions wether this be at receptor, DNA or mRNA level

Question 11

Assay development

Answer 11

• think of cost and reproducability
• relevance of assay
• quality of assay

Question 12

What is a hit?

Answer 12

a drug that can activate with affinity

Question 13

Screening compound library

Answer 13

look for downstream signalling
any signs that compound has effect on pathway
rapid screen of thousands of molecules but cant tell you if it will be good drug
inexpensive and easy

Question 14

Target drug design

Answer 14

You already know the target and you can judge the peptide to see if it will be a good drug

Question 15

Good peptide for drug

Answer 15

boost or replace endogenous signalling
know the function of the protein in the disease
no off target effects

Question 16

Bad peptide for a drug

Answer 16

difficult to administer
expensive of hard to manufacture
rapid in vivo degradation
immunogenic

Question 17

What is serendipity?

Answer 17

you accidentally discover a drug

Question 18

Penicillin

Answer 18

alexander flemings staphylococcus culture was contimated by a mould which made a bacteria free circle

Question 19

Farming existing knowledge

Answer 19

natural remedies

Question 20

After identification?

Answer 20

cell based assay or animal models to look at how the drug would work in humans

Question 21

Phase one trails

Answer 21

• permission required
• tested on less than 100 volunteers
• look at dangerous side effects, tolerability and pharmacokinetics

Question 22

Northwick park drug trail

Answer 22

• trail for b cell chronic lymphoid leukaemia and rheumatoid arthritis
• was big in ensuring safety in trails
• 6 volunteers had severe reactions
• new guideline

Question 23

Phase 2 trails

Answer 23

• check efficacy of drug in small group of patients
• dose response calculated
• group of patients at same progression in disease

Question 24

What percent of compounds make it past phase 2?

Answer 24

31%

Question 25

Tirasemtiv

Answer 25

- thought to treat ALS and MND - improve contraction of muscle in response to diminished neural imput - phase two it worked and muscle strength increased - phase three not well tolerated

Question 26

Phase three trails

Answer 26

- definitive randomised double blind placebo controlled trails - expensive - go to market if passed

Question 27

Phase four trails

Answer 27

- looking at the long term side effects - usually after its gone to market

Question 28

congenital malformations

Answer 28

abnormalitites that are present at birth

Question 29

teratology

Answer 29

study of abnormal development and causes of congenital malformations

Question 30

teratogen

Answer 30

an agent that induces congenital malformations

Question 31

example of drug pregnant

Answer 31

thalidomide

Question 32

how many infants effected by thalidomide

Answer 32

7000

Question 33

when was thalidomide discontinued

Answer 33

1961

Question 34

what did thalidomide cause

Answer 34

meromelia, heart alimentary and GU defects