Pharmaceuticals

3. Drug Design, Discovery and
Development
Saffron Pharmaceuticals (Pvt.) Ltd.
19 Km. Sheikhupura Road, Faisalabad-Pakistan.
• Presented by:
Dr. Yasir Mehmood
PhD Pharmaceutics,
MBA (Health
management)
• Head QA & VIRAC

4. DrugDiscovery&Development
Identifydisease
Isolateprotein
involvedin
disease(2-5years)
Finda drug effective
against disease
protein (2-5years)
Preclinical testing
(1-3years)
Formulation
Human clinical
trials (2-10years)
Scale-up
FDA
approval
(2-3years)
Anew drug currently costs ~$880million and
takes~15-16 years to develop

5. Drug design
Characteristics of ideal
drug

6. Lead compound
• A lead Compound is also known as a
parent compound.
• A lead compound is a compound having
a particular biological activity obtained
either from natural or synthetic source.
• E.g. Penicillin G, Prontosil

7. Drug design
Drug design may be defined as an effort to develop
a drug by molecular modification of lead compound
for optimization of desired effects and minimization
of side effects

8. 1. Choose a disease
2. Choose a drug target
3. Identify a bioassay
5. Isolate and purify the
lead compound if
necessary
4. Find a ‘lead compound’
8. Identify the
pharmacophore
7. Identify structure-
activity relationships
(SARs)
6. Determine the
structure of the lead
compound
9. Improve target
interactions
Stages required in drug design and drug discovery

9. 1. Rational Drug Design
2. Computer-assisted
Drug Design (CADD)
3. Neural network in Drug
Design
Types of drug design

10. 1-Rationale drug design
In contrast to traditional method of drug
discovery, which relay on trial and error testing
of chemical substances on cultured cells or
animals and matching the apparent effect of
treatment, rationale drug design begins with the
hypothesis that modulation of specific biologic
targets may have therapeutic value
It is a process in which finding a new
medication bases on knowledge of biological
target is done. It involves design of small
molecule that are complementary in shape and
charge to biomolecular targets

11. 2-Computer-aided drug
design
 CADD represents computational
methods and resources that are used
to facilitate the design and discovery
of new therapeutic solutions.

12. 1
Hit identification using virtual
screening (structure- or ligand-
based design)
2
Hit-to-lead optimization of
affinity and selectivity (structure-
based design, QSAR, etc.)
3 Lead optimization: optimization
of other pharmaceutical
properties while maintaining
affinity
Drug design with the help
of computers may be used
at any of the following
stages of drug discovery:
2- Introduction to CADD

13. 2- Computer-aided drug design

14. 3D models of membrane receptors can be refined and validated
in a realistic lipid- water-salt environment using molecular
dynamics simulations

15. 01
02
03
Data from virtual screening
can be used to develop
predictive models in order to
optimize ADMET properties
of the candidate molecules
The ultimate goal of this
procedure is to find investing
lead molecules that are worth
for further drug research and
synthesis
Virtual screening is a
computational technique
to find novel drug
candidates
Applications of computer-aided
drug design

16. • InSilicoisanexpressionusedto mean“performed
oncomputer or viacomputer simulation.”
• In Silico drug designing is defined as the
identification of the drug target molecule by
employingbioinformatics tools.
In silico drug designing

17. 1- Ligand base drug
designing
2- Structure-based Drug
Design
Types of in silico drug designing

18. Ligandbaseddrugdesign
• Ligand-baseddrug designrelies on
knowledgeof other moleculesthat bind to
the biological target ofinterest
• Used to derive a pharmacophore
Atom
based
Atom based + atom-typing
(Atomic, elemental,
pharmacophore like)
Pharmacophore
feature

19. TRADITIONAL DRUG DESIGN
(Pharmacophore-based drug design)
Lead generation:
Natural ligand / Screening
Biological Testing
Synthesis of New
Compounds by molecular
modification of leads
Drug Design Cycle
If promising
Pre-Clinical Studies

20. 2-NMRspectroscopy
3- Homologymodeling
1- X-ray
ceystalography
Structure-baseddrugdesign reliesonknowledge
of the three dimensionalstructure of the
biologicaltarget obtainedthroughmethods
suchas
Structure baseddrugdesign

21. Structure-based Drug Design (SBDD) or
Target-based approach
Molecular Biology & Protein Chemistry
3D Structure Determination of Target
and Target-Ligand Complex
Modelling
Structure Analysis
and Compound Design
Biological Testing
Synthesis of New Compounds
If promising
Pre-Clinical
Studies
Drug Design Cycle
Natural ligand / Screening

22. In silico drug designing

23. BasicStepsin In SilicoDrugDesigining

25. • Dockingis anattempttofindthebestmatchingbetweentwomolecules.
• Amoreseriousdefinition….
Dockingis amethodwhichpredicts thepreferred orientation of oneligand
when bound inanactive sitetoformastablecomplex.
Molecular docking
Target Ligand Molecular docking

26. 01 02 03
This is the most latest
technique being
applied to discover
new drugs. It works
on the same
principles as the
neural networks
found in the human
brain
This technique
makes use of
Computer Artificial
Intelligence, whereby
a computer learns by
itself, how to
approach a target
drug molecule and
improves its iterations
by itself
This technique can
be applied to solve
complex drug
calculations. Desktop
computers as well as
Super-Computers
both are employed for
Neural Networks
Drug research
3- Neural network in Drug Design

27. Serendipity
Acetanilide →
Antipyretic
Penicillin →
Antibacterial
Piperazine →
Anthelmentic
Serendipity is defined as
valuable discoveries
accidentally, luckily or
suddenly by Pharmacists,
Chemists, Physicians & other
investigators

28.  A patient with infection (intestinal parasite) was
supposed to be given Napthalone. But he was
given accidentally acetanilide, and fever of the
patient was reduced. Thus, acetanilide was
accidentally discovered as an antipyretic agent.
However, now a day, it is not used as antipyretic
due to its nephro toxicity
Acetanilide as Antipyretic
 The antibacterial action was introduced
accidentally by Flemming in 1920 while he was
working with a bacterial culture, the culture was
contaminated with penicillium fungi, which
destroyed the cultured bacteria in the medium. In
further stage, the active component penicillin was
isolated form the respective fungi
Penicillin as Antibiotic
Serendipity

29. It is an effort to produce new drug
molecules from a lead compound
by applying variety of approaches
of design. Drug design
approach is the prerequisite for
drug discovery
Drug discovery

30. History of drug discovery
Pre 1919
• Herbal Drugs
• Serendiptious
discoveries
1920s, 30s
• Vitamins
• Vaccines
1940s
• Antibiotic Era
• R&D Boost due to
WW2
1950s
• New technology,
• Discovery of DNA
1960s
• Breakthrough in
Etiology
1970s
• Rise of
Biotechnology
• Use of IT
1980s
• Commercialization of
Drug Discovery
• Combinatorial
Chemistry
1990s
• Robotics
• Automation

31. Drug discovery process

32. Drug discovery cycle

33. Drug Development
Drug development or preclinical development
is defined in many pharmaceutical companies
as the process of taking a new chemical lead
through the stages necessary to allow it to be
tested in human clinical trials, although a
broader definition would encompass the
entire process of drug discovery and clinical
testing of novel drug candidates.
33
19 March 2009

34. Pharmaceutical development
•
– The aim of pharmaceutical development is to design a quality product
and its manufacturing process to consistently deliver the intended
performance of the product.
– Scope:
• Drug product submission for marketing authorisation
• Not: pharmacy-prepared drug products
• Not: IMPs
34
ICH Q8 (R2) (EMEA/CHMP/167068/2004)

35. Development policy
• Develop local "pharmaceutical development procedure"
• This procedure should cover:
– scope
• magistral or officinal preparations - reconstitution
– pharmacotherapeutic aspects
– technological aspects
– product file & review & approval
– clinical evaluation
– Product Quality Review
35

36. 6
5
4
3
2
1
Toxicological
evaluation
Carry out
clinical trials
Make money
Improve
pharmacokinetic
properties (ADME)
Design a
manufacturing
process
Market the
drug
Stages required in drug development

37. Stomach
pH2
Intestine
pH3-8
PV
Blood Kidneys Tissues Cell
Target
Stability
Acidic
enzymatic
buffer
Solubility
pKa
Stability
CYP3A
metabolic
stability
Permeability
Passive
P-gp efflux
Transportes Log
Liver
Phase I and II
Metabolic
stability
Metabolite ID Protein
binding RBC
uptake
Stability
Enzymatic
Plasma
stability
37
Renal
Extraction
Log D
Permeability
Passive
Transporters
Log D
Cell Exposure
Barriers of Drug Reaching Target
Stability
Acidic
buffer

38. Candidate Selection: Building “Developability” in
Preclinical Profiling
Lead (active
molecule)
Metabolism
Selectivity
Potency
(optimized molecule)
Physical properties
Potency
Selectivity
Metabolism
Best leads
Physical / chemical
properties
Biopharmaceutics

39. 1- Integrity
8- Polymorphism
4- Log D
5-pKa
3- Permeability
6-Stability
2- Solubility
7- Lipophilicity
Lorem Ipsum
Physico-chemical profile of NCEs

40. Drug Delivery
40
19 March 2009 KLE College of Pharmacy, Belgaum
 Drug delivery is the method or process of administering a
pharmaceutical compound to achieve a therapeutic effect
in humans or animals
 Drug Delivery technologies are patent protected
formulation technologies that modifies drug release
profile, absorption, distribution and elimination for the
benefit of improving product efficacy & safety and patient
convenience & compliance

41. Drug Delivery
 Drug delivery is the method or
process of administering a
pharmaceutical compound to
achieve a therapeutic effect in
humans or animals

42. Veginal DDS 06
Buccal DDS
08
Nasal DDS 04
Topical
DDS 03
Oral DDS 01
LOREM
IPSUM
LOREM
IPSUM
Drug Delivery Systems