Download target

….still is a very wealthy business.
From US Pharmaceutical Industry Report, 2008-2009
• The United States has the largest pharmaceutical industry in the world.
In 2007, its pharmaceutical revenue totaled at US$ 315 billion.
• Pharmaceutical R & D expenditure has been maintaining an increase,
even in 2008, impacted by the global financial crisis, the
pharmaceutical R & D expenditure increased by 3.16% from last year.
• There are 2,900 drugs currently in research in US, among which 750
are anticancer drugs, 312 drugs are for heart diseases, 150 are diabetes
drugs and 109 are AIDS drugs, etc.
• In 2009, the sales growth of drugs in the United States is expected to
around 1% ~ 2%.
The Drug Discovery Process
I
D
E
A
Exploratory
research
Therapeutic
research
Exploratory
development
The strategy
Full
development
D
R
U
G
The Initial Approach to Drug Discovery
- Pharmacology-to-Target -
Defined Biological
Endpoint
(e.g., bacterial
growth)
Identification
of MoA
Identification
of active
compound
Target
•SAR Analysis
•Therapeutic Index
•Pharmacokinetics
Additional
•SAR Analysis
• Therapeutic Index
•Pharmacokinetics
Evolution of the approach
- Protein (target)-to-Gene Enzyme/
Receptor
of Interest
High-Throughput
Screening Assays
Established against
Target Protein
Isolation/
Characterization/
Purification of
Target Molecule
Identify Lead.
Confirm Role in
Disease Process.
Gene Cloning/
Sequencing. Recombinant
System generation
•SAR Analysis
•Therapeutic Index
•Pharmacokinetics
A New Paradigm for Drug Discovery
- Gene-to-Function Gene of
Unknown
Function
Determination of
Cellular Function
High-Throughput
Screening Assays
Established against
Target Protein
Validation as an
Attractive Drug
Target
Identify Lead
Inhibitor
Expression/
Protein
Purification
Chemical StructureActivity Analysis
•Therapeutic Index
•Pharmacokinetics
Questions???
R&D process for a new drug
TARGET
I
D
E
A
Exploratory
research
CANDIDATE
Therapeutic
research
Exploratory
development
POC
Full
development
Target selection, identification and validation
D
R
U
G
What is a target?
• The target is a molecular entity that
appropriately stimulated or inhibited
could positively modify the initiation
or outcome of a pathology
Target selection
Target selection:
the decisional hierarchy
Knowles and Gromo, Nature Rev Drug Disc 2002
Target selection
Origin of new targets
The process that lead to the discovery of
a new drug starts from the study
of pathology’s molecular basis
Cellular and
Molecular biology
Biochemistry and
Pharmacology
Target
Genetics
Physiology
Clinical observations
Target selection
The type of target influence
the type of drug
• Main drugs’ categories
– Small molecules
– Biologicals (e.g. antibodies, hormones, etc)
• The drug discovery process for the two categories
of drugs is not exactly the same
• In the rest of the presentation we will mainly focus
on that for small molecules