CSB202: Lecture 14 - Drug Discovery

drug

substance that, when absorbed into the body of a living organism, alters normal bodily function

medication drug

chemical substance used in the treatment, cure, prevention or diagnosis of disease or used to otherwise physical or mental well-being

big 5 criteria

1. effective (treat/cure/prevent a disease)

2. safe (few side effects)

3. absorbed into the body (pill, injection, etc)

4. get distributed to the proper part of the body

5. removed from the body (liver, kidney, etc)

drugs typically work

by inhibiting or activating proteins

how are drugs made?

1. discovery (2-10 years)

2. preclincal (lab & animal) testing

3. phase I

4. phase II

5. phase III

6. FDA review & approval

7. postmarketing testing

discovery

1. basic scientific research: finding out why problem occurs

2. target identification: what protein do we want to activate or inactivate for treatment

3. assay development: create a test to detect chemicals that activate or inactivate the target

4. screening: test millions of chemicals using the developed assay

5. optimization: take the best chemical and see if you can alter it to make it more effective or safe

assay development

1. add protein to wells plate

2. add compounds (1 per well)

3. detect protein activity

use robots to automate this

preclinical

1. good laboratory practices: agencies ensure that rules are followed for consistency and reliability

2. pharmacodynamics: studying the effect of the potential drug on animal bodies and how much of the drug is needed/safe

3. pharmocokinetics: studying absorption, distribution, metabolism, excretion

phase I clinical trials

• 20 - 30 healthy volunteers

• check for safety and dosage

• not for an effect

phase II clinical trials

• 100 - 300 patient volunteers

• test for efficacy and side effects

phase III clinical trials

• 1000 - 1500 patient volunteers

• test long term effects of drug use

FDA review and approval

• submit to FDA for approval

• may require further testing

post market testing

continually monitor patients taking the drugs for rare side effects

placebos

have a big effect, if you believe it will work, it will work

repurpose

• failed drugs can be repurposed (more likely than not, they will fail at one of the steps)

• ie. viagara was originally a hypertension drug → better for ED

• save time and money as drug has already progressed through some steps

herbalism

• traditional medicinal or folk medicine practice based on the use of plants and plant extracts

• may have an adverse effect or none at all

• but 25% of modern drugs have been derived from plants but they have been tested for safety and efficacy