THE QUEST FOR THE CURE

THE DRUG DISCOVERY CRISIS

Are we running out of drugs??

HOW DO DRUGS WORK

DIAZEPAM

PROZAC

IBUPROFEN

OMEPRAZOL

Most drugs (their active principle) are small molecules

ATORVASTATIN

DRUGS OF ABUSE

Morphine

Heroine (Bayer, 1874)

Cocaine

Cannabinol (THC)

The active principle is also a small moleculeAddiction as a side effect makes them not useful

HOW DO DRUGS WORKDrugs work by binding to specific proteins (enzymes) and modifying their activity

The selectivity of a drug in provided by the 3D structure of the target protein

Besides the large number of drugs available, only 2% of the human proteins are known to targeted by the drugs

Antibiotics and antivirals are drugs that inhibit bacterial and viral proteins, while leave ours untouched

Protein

HOW NEW DRUGS ARE DISCOVERED

In the past:

• by identifying the active ingredient from traditional remedies (plant extracts…etc. )

• by serendipitous discovery (e.g. penicillin, benzodiazepines)

Nowadays:

• Large scale testing of chemical collections • Rational design

HOW NEW DRUGS ARE DISCOVERED

Development of an assay for the desired activity

Screening thousand of compounds

Preclinical & clinical studies

Rational design based on :• Structure of the target.• Modification of known drugs

Target candidate

Basic Science

STAGES IN THE DRUG DISCOVERY PROCESS

Food and Drug Administration (FDA) in the United States (or comparable agency in other countries)

Lombardino & Lowe. Nature Reviews Drug Discovery (2004) 3, 853-862

The development of a new drug can take several decades and billion dollars invested

Target selection

THE DRUG DISCOVERY CRISIS

Are we running out of drugs??

• The better understanding of human biology will offer new candidates to find drugs(We must support basic research!!!)

• New technologies for the rational design of drugsare in development. They will reduce costs and will provide new medicines.

• There is little knowledge yet about how drugs interact.

• Gene therapy methods will join the “small molecule”toolbox once their safety is assured.

The future