Drug Discovery Process Massimiliano Beltramo, PhD
Drug Discovery ProcessAim of the two lessons:
To give an overview of the drug discovery process.
At the end of the lessons you will gain a general idea of the steps necessary to move a new drug from the bench to the bedside.Lesson I outline:General notions about drugs and the drug discovery processTarget selection/identification/validationLesson II outline:Target validationAssay development and screeningLead identification/selectionPreclinical developmentClinical development
What is a drug?In pharmacology, a drug is "a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being.
Various types of drugsDrugs that interfere with the cause of the disease disease modifying agents Their action is intended to remove the cause of the disease (antibacterial, antivirals, vaccines, etc)
Drugs which compensate for deficitsInsulin, vitamins therapy, etc
Drugs which alleviate the symptoms Symptomatic treatments (analgesic, antiallergic, etc)
Various classes of drugsNatural productplant extracts animal fluids (e.g., snake venoms)
Synthetic small moleculesMedicinal chemistry derivedCombinatorial chemistry derived
BiologicalsNatural products (isolation)Recombinant productsChimeric or novel recombinant products
To address unmet medical needs
A new drug: why? To reduce social cost of diseases To improve the quality of life
Unmet Medical Need
Disease associated costsThe medical care costs in USA in 2005 were around $2 trillion.
Direct costs are those connected with the use of medical care in the prevention, diagnosis, and treatment of disease and in the continuing care, rehabilitation, or terminal care of patients. Examples include: expenditures for hospitalization,drugsoutpatient clinical care, nursing home care, services of primary physicians and specialists, etc
Indirect costs measure the value of time that patients lose from employment or other productive activity due to mortality or morbidity. These costs also include reduced productivity once the patient returns to work, including unwanted job changes and loss of opportunities for promotion or education
Burden of illness exceeds economic costs. Estimates of the economic costs of illness do not capture some important aspects of the burden of illness such as reduced functioning, pain and suffering, and deterioration in other dimensions of health-related quality of life including emotional and psychological impacts on families, friends, and co-workers.(Source: NIH)
The first pharmaceutical researcherFirst drugs were of natural origin:herbs, seeds, fruits, roots, part of animals, rites and ceremonies
The Drug Discovery Today
The Drug Discovery Process
The whole process takes between 10 to 15 years.R&D timing
High risk activity Only 25 out of 100 new chemical entities (NCEs) tested in man reach the marketTarget-Related Failures(35%)Successful NCE(25%)Metabolism Failures(10%)Pharmacokinetic Failures(10%)Toxicity Failures(10%)Other Failures(10%)
Increase of R&D costs to develop a drugIn 17 years (1986-2003) the cost to develop a drug is increased more then ten times.
Drugs withdrawn from the market