2. THE DRUG DISCOVERY CRISIS Are we running out of drugs??
3. HOW DO DRUGS WORK Most drugs (their active principle) are small molecules OMEPRAZOLDIAZEPAM IBUPROFEN PROZAC ATORVASTATIN
4. DRUGS OF ABUSE C o c a i n e Morphine Cannabinol (THC)Heroine (Bayer, 1874) The active principle is also a small molecule Addiction as a side effect makes them not useful
5. HOW DO DRUGS WORKProtein Drugs 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 Antibiotics and antivirals are drugs that inhibit bacterial and viral proteins, while leave ours untouched Besides the large number of drugs available, only 2% of the human proteins are known to targeted by the drugs
6. HOW NEW DRUGS ARE DISCOVEREDIn 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
7. HOW NEW DRUGS ARE DISCOVEREDBasic Science Screening thousand of compounds Target Development of an assay candidate for the desired activity Preclinical & clinical studies Rational design based on : • Structure of the target. • Modification of known drugs
8. STAGES IN THE DRUG DISCOVERY PROCESSTarget selection Food and Drug Administration (FDA) in the United States (or comparable agency in other countries) The development of a new drug can take several decades and billion dollars invested Lombardino & Lowe. Nature Reviews Drug Discovery (2004) 3, 853-862
9. THE DRUG DISCOVERY CRISIS The future • The better understanding of human biology will offer new candidates to find drugsAre we running out of drugs?? (We must support basic research!!!) • New technologies for the rational design of drugs are 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.