Drug development and sources of drugs

How many years does it take for the development of one drug?

10-15 years

Cost to develop a drug

around 2 billion pounds

What does FDA stand for and where is it used?

Food and drug administration and used in USA

What does EMA stand for and where is it used?

European Medicines Agency and used in Europe

What is the main purpose of the FDA and EMA?

Provide approval to market and supply a drug

Name the drug development stages

1) biological target identification

2) hit molecule identification

3) development of hit molecule to lead molecule

4) lead molecule optimisation

5) candidate selection / pcs

6) clinical trials

What happens in biological target identification?

Find which protein or receptor causes the disease

What happens in hit molecule identification?

Find molecules that work / starting point

~ high throughput sequencing

~ natural sources / animal / marine

~ venom / toxins

~ medical folklore

~ accidental

What happens in hit to lead?

Improve the best drugs found

Structure activity relationship

Which part of molecule matter for activity

SAR

changing different parts of a molecule and observing how these changes affect its biological activity

Whilst reducing toxicity

what happens in lead optimisation?

Have around 5 molecules and make them better by improving potency, solubility and stability

What happens in candidate selection?

List tests / trials they do

One molecule selected for pcs

Test on cells (in vitro)

Test on animals ( in vivo)

Test for acute toxicity and long term toxicity

Test to see any effect on cell reproduction/ see any carcinogens prevent further development

What approval is needed before doing clinical trials on humans?

Regulatory approval

FDA or EMA

EMEA = evaluation of medicinal products in Europe

Who gets tested in clinical trials?

Humans

Explain why the three-dimensional structure of a drug molecule can affect its interaction with a biological target

A drug's three-dimensional shape and stereochemistry affect how it fits and binds to its biological target. Different spatial arrangements can interact differently with the target, potentially changing the drug's activity or toxicity.

What does NICE stand for

National institute for health and care excellence

Which country is NICE used in

UK

What is the role of NICE?

Cost vs benefit analysis on drug

Decides if NHS can pay for drugs and if they can be prescribed

Example of drug NICE have not approved

Anticancer drug Kadcyla

90k per patient

What is a patent?

Only pharmaceutical company have exclusive rights to sell and manufacture its products

What happens when a patent expires?

Other companies can make and sell the drug

Becomes a generic drug

Prodrug

Inactive until metabolised

What is chemoinformatics?

Computers used to store data

Predict drug activity

Toxicity

Predict compounds / potential active compounds

Look at chemical structure and link to activity and toxicity

Ways computers used for drug development

~ Store chemical information

~ computational libraries ( info drug structure/ prop/ activities see any adverse reactions / therapeutic target

~ computer aided drug design

~ molecular modelling

~ virtual screening

Can computers be used to find new use for existing drugs?

Yes done via virtual screening of drug to see if they can cr as possible treatments

Molecular modelling ADMET

Absorption

Distribution

Metabolism

Excretion

Toxicity

Advantages of chemoinformatics

Fast

Low cost

Reduce animal testing

Rapid identification

Eliminate unsuitable candidates

Handle large amounts of data

Only need knowledge of structure

Disadvantages of chemoinformatics

Inaccurate prediction

Complex software

Shouldn’t just rely on chemoinformatics

Definition of pharmocognosy

Knowledge of medicinal drugs from plants or other natural sources

Where they come from, the structure, function, toxicity, economic importance

What is St John’s Wort?

Herbal medicine

Interacts with many medications

Multiple active ingredients

What is a natural product?

Secondary metabolite

Produced by organism

Lead to enhanced survival traits but not needed for survival

What is primary metabolites?

Involved in growth development and reproduction.

Physiological function

,any organisms

No pharmacological action

Example primary metabolites

Amino acids

Proteins

Sugar

Organic acids

What is a secondary metabolite?

Shows pharmacological action

Not involved in development growth and reproduction

Limited organisms

Ecological function

Example of secondary metabolites

Alkaloids

Terpenes (isoprene units)

Glycosides

Steroids (biosynthesis squalene)

Phenolics

Alkaloid example

Morphine from opium poppy

Opium gets 12% morphine

Quinine used for malaria

Ergotamine ergot fungus for migraine and childbirth induce

Glycoside examples

Salicin reduce inflammation

Digoxin foxglove heart rate

Phenolic example

Warfarin

How often does the WHO essentials medicine list get updated?

Every 2 years since 1977

What is essential medicines?

Drugs that satisfy health care needs of majority of population

Drugs on WHO essentials medicine list

Morphine

Quinine

Colchicine

Atropine

Anticancer drug example

Mustard gas decrease white blood cell count

Nitrogen mustard used for anti tumor activity

Serendipity

Finding a drug by accident

Premarin ( biological natural source)

Conjugated oestrogens

Treat hrt post menopausal

Prevent osteoporosis

Pregnant mare urine

Pregonal

LH and FSH

Treat infertility

From urine of post menopausal women

Hyaluronic acid

Treat osteoarthritis of knee

From chicken comb

Exenatide (byetta)

Treat type 2 diabetes

From saliva of gila monster

Paclitaxel

Anticancer drug

Pacific yew tree

1g from 3× 100 year old trees

Synthetic drug

Man made from chemicals that are oil based

E.g paracetamol

Semi synthetic

Starts as natural substance then modified in lab