drug discovery Flashcards
natural products
many natural products have been isolated and studied
morphine from opium
cocaine from cocoa leaves
quinine from bark of cinchona tree
how much discovery , design and devlopment for one drugs?
for one drug can take 10-15 years
sysnthesis of 10,000 compounds and 2 billion dollar cost
how is a disease in a body caused
diseases is caused when a process in the body has stopped working, has deviated from its original purpose or become overactive.
drug discover first step
Biological target identification
when a protien becomes upregulated, down regulated or inactivated , researchers will work to identify such protiens to fund a cure or how to control the disease. so many scientific experiments are carried out to make sure that its worth pursuing the target.
targets can also be chosen following the discovery of the mechanism of action of other drugs
what is the second step
hit molecule identification:
researchers use several techniques to identify a chemicals starting point.
1. HTS high through put screening :this is where thousands of compounds are assayed against the target of interest to see if any molecules interact with this protein.
2. natural products: purified organic compounds isolated from natural sources that are produced by the pathways of primary or secondary metabolism . they have no biological responsibility in the host organism but can lead to enhanced survival traits
3. medical folkore: most these treatments were found not to work but there has been some therapeutic effect eg rhubarb root
4. natural ligands:biological chemicals which naturally interact with the protien can be modified chemically to generate new hits eg adrnaline and nor adrenaline were the starting points of adrenergic b agonist
5.existing drugs: they may be drugs on the market already which interact with the protein but require some modification eg a compound has properties of a oral absorption but to avoid toxic effect inhaled compound is more effective
6. enhancing a side effect
7. computer aided designs
8. serendipity : a ship carrying mustard gas exploded and ppl who inhaled gas lost their white blood cells this was then optimised to be used for treatments with leaukemia
is a computer allowed to market the same compound
a company is not allowed to market the same compound which shares the same structure of another company until the potent has expired
but can market a compound which acts at the same biological target
what is the stage 3
this is the development of hit molecule to lead molecule.
one the hit chemical is identified chemists work to synthesis compounds with same structures to build up a picture of which aspects of the molecule are required for activity this is called SARS- STRUCTURE ACTIVITY RELATIONSHIPS
the scientist will then try to make a potent compound or a compound with desirable properties eg water solubility. stability in human body . some compound may already be present with these properties.
what is stage 4
lead molecule optimisation
after further optimisation and synthesis of analogues it will result in the identification of 5 molecules which exhibit all of the desired properties . this molecule may not be perfect at this point but will have an acceptable balance between potency and desired physical properties. hundreds of compounds may be synthesised at the stage
5th stage of drugs
candidate selection a molecule is tested for PCS.
PCS- pre clinical safety
at this stage the toxicity of the molecule is tested
- at first in vitro tests on cells or in vivo tests on animals are done to find out whether the compound has any effect on cell reproduction , if it causes cancer etc .
- the drug will also be tested for acute toxicity , this is done by administration of large doses to find out what the toxic level / lethal level is of the compound. and different animals will be used and dissected to test whether particular organs are affected
- then long term toxicity test on animals will be carried out over a period of years to test a drug for chronic toxic effects.
many drugs fail the toxicity test
what happens after pcs?
in order to use the drugs on humans it must be approved by the regulatory body the FDA or EMEA .
before clinical trial begins any adverse reaction during clinical trials is sent to regulatory body
and if the trial has run smooth ans NDA to fda is made
and Maa to emea is made
NDA (new drug application) AND MAA ( marketing authorization application)| are large documents containing all the data from the research, , clinical trials and pcs
what is a clinical trial ?
after pcs and the drug is not toxic to humans and regulatory body has given approval clinical trials will begin in 3 stages
Phase 1: drug is tested on a set of healthy volunteers 20-80 ppl. to ensure the safety , efficacy , side effects
phase 2: given to patients usually 100-300 ppl to see if its effective, optimal dose and short term safety
phase 3: a large amount of amount 1000-3000 this takes a longer time and usually is done to confirm safety and effectiveness
can be sent to fda for approval after this process
what is NICE?
It is a . national institute for health and clinical excellence.
what is the final hurdle in Uk
before it reached the market in the Uk and before it can be prescribed , cost vs analysis is carried out by NICE,
they will decide whether the nhs should pay for these drugs and prescribe to patients .
what is patents?
Pharmaceutical companies will have spent alot of time and money on research and development and will wants to reap the benefit of hard work
so they seek permission to have exclusive rights to sell and manufacture products through applying for a patent
patent: it means being the sole owner for years but you have give a clear and detailed public disclosures of the invention to the gov
once the patent expired other companies will be allowed to make distribute the drug
what are primary metabolites?
directly involved in normal growth , development and reproduction
it performs a physiological
function in the organism
present in many organism and doesnt show its pharmacological actions
eg amino acids, proteins , sugars, organic acids
