Introduction, Types and Drug Development.

1. DRUG DESIGNING
Presented By:
Paarsa Hassan
Zainab Nooruddin
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2. INTRODUCTION
• Chemical or biological substances.
• Single compounds or a mixture of different
compounds.
• In the past, treatment through traditional remedies.
• Present day, diseases are cured on molecular levels.
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3. HISTORY
– Plants or Natural Product
• Plant and Natural products were source for
medical substance
• Example: foxglove used to treat congestive heart
failure
– Accidental Observations
• 1928: Alexander Fleming observed the effect of
mold
• Mold (Penicillium) produce substance penicillin
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5. DRUG TARGETS
• Target  Molecular recognition site to which drug
binds
• Target may be
– Protein molecule
 A receptor
 Enzyme
 Transport molecule
 Ion channel
 Tubulin
 Immunophilin
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7. TYPES
There are four different methodologies commonly used
in the drug designing:
1) Ligand-Based Drug Design or Indirect Drug
Design
2) Structure-Based Drug Design or Direct Drug
Design
3) Rational Drug Design
4) Computer-Assisted Drug Design
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8. Mechanism Based Drug Design
• When the disease process is understood at the
molecular level and the target molecule(s) are
defined
• Drugs can be designed specifically to interact with
the target molecule in such a way as to disrupt the
disease.
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9. Structure-Based Drug Design
• First techniques to be used in drug design.
• Helped in the discovery process of new drugs.
• Information about the structural dynamics and
electronic properties about ligands are obtained
from calculations.
• Structure-based drug design can be divided roughly
into two categories:
I. Ligand based
II. Receptor Based
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• The first category is about “finding” ligands for a
given receptor.
• A large number of potential ligand molecules are
screened
• This method is usually referred as ligand-based
drug design.
• It saves synthetic effort to obtain new lead
compounds.
Ligand-Based Drug Design

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12. What is Docking?
• Docking attempts to find the “best” matching
between two molecules
• It includes finding the Right Key for the Lock
• Given two biological molecules determine:
- Whether the two molecules “interact”
- If so, what is the orientation that maximizes
the “interaction” while minimizing the total
“energy” of the complex
Goal: To be able to search a database of
molecular structures and retrieve all molecules
that can interact with the query structure
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13. Receptor Based Drug Design
• Another category is about “building” ligands, which
is usually referred as receptor-based drug design.
• Ligand molecules are built up within the constraints
of the binding pocket by assembling small pieces in
a stepwise manner.
• These pieces can be either individual atoms or
molecular fragments.
• The key advantage of such a method is that novel
structures, not contained in any database, can be
suggested.
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Computer Aided Design

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Techniques of Drug Design

17. • Starting point for gathering information from
mechanistic drug design.
• Determine structural information about a molecule.
• Provides the critically important coordinates needed
for the handling of data by computer modeling
system.
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X-Ray Crystallography

18. Nuclear Magnetic Resonance (NMR)
• NMR uses much softer radiation
• Examine molecules in the more mobile liquid phase
• Three-dimensional information will be obtained.
• Examines small molecule-macromolecule complexes.
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19. Homology Modeling
• Homology modeling, also known as comparative
modeling of protein.
• Constructing an atomic-resolution model of the
"target" and an experimental three-dimensional
structure of a related homologous protein.
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Computer Aided Drug Design

21. HOW IS A DRUG DEVELOPED?
• The development of a new therapeutic drug is a:
I. Complex
II. Lengthy
III. Expensive
• It can take 10-15 years
• Over $500 million to develop a drug from an
initial concept.
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22. Identify Disease
Isolate Protein
(2-5 years)
Find a Drug
(2-5 years)
Preclinical testing
(1-3 years)
Human clinical trials
(2-10 years)
FDA approval
(2-3 years)

23. Identify Disease
Isolate Protein
Finding Drug
Preclinical Testing
TARGET SELECTION
LEAD DISCOVERY
MOLECULAR MODELING
VIRTUAL SCREENING
COMBINATORIAL CHEMISTRY
IN VITRO & IN SILICO ADME MODELS
Cellular & Genetic Targets
High Throughput Screening
In-silico Screening
Chemical Synthesis
Computer graphics & models help improve activity
Tissue and computer models begin to replace animal testing
Human Clinical Trials

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25. CONCLUSION
 Drug Designing is a multidisciplinary, complex,
costly and intellect intensive process.
 Modern drug design techniques can make drug
discovery process more fruitful & rational.
 Knowledge management and technique specific
expertise can save time & cost, which is a
paramount need of the hour.
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26. REFERENCES
• http://www.yourgenome.org/facts/how-
are-drugs-designed-and-developed
• http://rxcinternational.com/different-types
• http://slideplayer.com/slide/10688957/
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THANK
YOU

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