LEARNING OBJECTIVES

1. Recognize, identify and discuss the importance of drugs

2. Discuss the development of pharmaceutical industry
3. Demonstrate knowledge on drug discovery and development
overview, ethnopharmacology, natural product research and
basic biology of disease
 DRUG DISCOVERY

• The process of drug discovery involves the identification of

lead and its targets, synthesis, characterization, screening, and
assays for therapeutic efficacy of lead.

• Once a compound has shown its value, it will begin the

process of drug development prior to clinical trails
 DRUG OVERVIEW
“Drug" means:
•Articles recognized in the official United States Pharmacopoeia,
official Homeopathic Pharmacopoeia of the United States, or
official National Formulary, or any supplement to any of them;
and
•Articles intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease in man or other animals; and
 DRUG OVERVIEW
“Drug" means:
•Articles (other than food) intended to affect the structure or any
function of the body of man or animals; and
•Articles intended for use as a component of any articles
specified in clauses (1), (2), or (3), but not include devices or
their components, parts, or accessories.
 PHARMACEUTICAL CENTURY
Patents & Potions

PATENT
• a government authority or license conferring a right or
title for a set period, especially the sole right to exclude
others from making, using, or selling an invention.

POTION
• a liquid with healing, magical, or poisonous properties
 PRESENT: DRUG DISCOVERY
• Begins in the laboratory with scientists of various functional areas
working together to identify cellular and genetic factors that play a role
in specific disease

PRE-DISCOVERY
• Understanding the disease
• Know the underlying cause for the disease
• Try to understand how genes are altered – how they affect proteins
they encode
• How proteins interact with each other in living cells
• How those affected cells change the specific tissue they are in
• FINALLY, how the disease affect the entire patient
The cinchona tree (left) and The common foxglove plant (Digitalis
quinine (right) were important purpurea, left) contains cardiac
players in the treatment of glycosides such as Digoxin (right),
malaria infection for over 300 which are known to increase cardiac
years. contractility via inhibition of myocardial
sodium/potassium ATPase.
 STEPS IN
DRUG
DISCOVERY
 STEPS IN DRUG DISCOVERY
1. Target Selection
2. Target Identification
3. Target Prioritization/ Validation
4. Lead Identification
5. Lead Optimization
 TARGET SELECTION
• defined as the decision to focus on finding an agent
with a particular biological action that is anticipated to
have therapeutic utility.
 PROTEIN
TARGET MOLECULE
Naturally existing cellular • Receptor
or molecular structure • Enzyme
involved in the disease • Transport molecule
pathology on which the • Ion channel
drug acts. • Tubulin
• Immunophilin
 TARGET IDENTIFICATION
Scientists use a variety Cellular and Genetic Targets
of techniques to identify
and isolate individual Genomics
targets to learn more
about their functions and Proteomics
how they influence
disease Bioinformatics
CELLULAR & GENOMICS
GENETIC TARGETS • The study of genes and their
function
• Involves identification of the target
• Exploit the findings from the
receptors or enzymes whereas for
sequencing of the human and
some biologic approaches the
other genomes to find new drug
focus is at the gene or
targets.
transcription level.
• Based on 5 or 10 linked
• Drugs usually act on the targets,
proteins per gene, proposes
which are associated with disease.
that the number of potential
drug targets may lie between
5,000 or 10,000.
PROTEOMICS BIOINFORMATICS
• “Proteome”
• It plays a key role in various
• It is also at the protein level
stages of the drug discovery
that disease processes
process including:
become manifest, and at which
• Target identification
most (91%) drugs act.
• Computer screening of
• Target identification with
chemical compounds
proteomics is performed by
• Pharmacogenomics
comparing the protein
expression levels in normal
and diseased tissues.
 TARGET VALIDATION
• Involves demonstrating that a molecular target is critically
involved in a disease process and modulation of the target
is likely to have a therapeutic effect.
• Experimental approach by which a “potential” drug target
can be tested and given further credibility.
 LEAD IDENTIFICATION
• A lead compound or substance is one that is believed to
have potential to treat disease.
No intellectualization and
RANDOM
assays

SCREENING
Also known as
 Investigation of a great
NON-RANDOM targeted/focused/more
number of compounds
narrow approach
for a particular problem
or feature of them
Whether the “hits” against the
CROSS chosen target will interfere
with other related targets.
 CONFIRMED VALIDATED
PRIMARY HIT
HIT HIT
 compound giving
positive result in a  compound is  compound hit that
screening assay confirmed as shows selective
positive when activity
assay is repeated

A compound that
HIT passes such a
“screen”
 LEAD OPTIMIZATION
• compares the properties of various lead compounds and
provides information to help biopharmaceutical companies
select the compound or compounds with the greatest potential
to be developed into safe and effective medicines
• The lead optimization cycle begins with the identification of a lead
structure (“hit”) in a relevant biological assay.
• New analogs with structural modifications are prepared and screened
in the biological assay.