mail for ppt jangraboys14@gamil.com

1. TARGET IDENTIFICATION &
VALIDATION
LEAD IDENTIFICATION &
OPTIMIZATION
Presented by :- sachin jangra
mPHARMA 2nd SEM
Roll no. 5461075

2.  Identifying the biological origin of the disease and
the potential targets for involvement ,is the first step
in the discovery of a medicine..
 Target identification is process of identifying the
direct molecular target(protein,nucleic acid, or small
molecule).
INTRODUCTION

3. Target
 Finding a protein or receptor associated
with the disease with which a potential
drug interact is known as the TARGET.
LEAD
A compound usually a small organic
molecule that reveal desired
biological
activity on a validated molecule
target.

4. Lead identification
/optimization is the one of most
important steps in drug
development. The chemical
structure of lead compound is
used as starting point for chemical
modification in order to improve
potency.

6. DRUG DISCOVERY PROCESS
 Process starts with the identification of a
molecular target & then Target validation.
 The target validation confirms that
interaction with the target produce the
desired change in the behaviour of
diseased cells.

7. Characteristics of DRUG TARGET
• The drug target is a biomolecule , normally a
protein that could exist in complex modality.
• The biomolecules have special sites that
match other molecule.
• Drug bind with the protein reversibly.
• Change in the biomolecule/protein structure
follow the physiological response.

8. Continue….
 The physiological response play a
major role in complex regulation &
have a therapeutic effect.
 Biomolecule’s activity, expression
& structure might change over
duration of pathological process.
 These small molecule bind to the
biomolecule are drugs.

9. Role of target identification
 A good target needs to be efficacious,
safe, meet clinical and commercial
needs and above all, be ‘druggable’.
 When a biological molecule elicit a
biological response which may be
measured both in vivo/vitro is known to
be a druggable target .
 A good target identification increased
confidence in the relationship between
target and disease.

10. Approaches to
target identification
1. Direct biochemical method
2. Computational inference
method
3. Genetic interaction method

11. Direct biochemical method
 Biochemical affinity provides the most
direct approach to finding target proteins
that bind small molecules of interest.
 Because they are based on physical
interactions involving mammalian or
human proteins, biochemical methods
can lead to information about molecular
mechanisms of efficacy.
 Direct detection of binding using some
washing procedure.

12. Computational inference method
Comparsion of small molecule to the
known reference molecule is done.

13. Genetic interfernce method
 Used to identify protien target .
 Aim of this method is to compare two
or more genomes in order to find the
similarities and differences
 Hence identify potential drug target.

14. Lead compound
• chemical compound that has
pharmacological or biological activity and
therapeutically useful are the LEAD
compound
• Organic compounds are identified which
interact with the target protein and
modulate its activity by using screening
approaches.
Lead identification

15. Methods of lead Identification
I)Random screening:
• All compounds including synthetic chemicals,
natural products of plant, marine and
microbial origin from a given series are
tested.
• Inspite of budgetary and manpower overuse,
this method may be used to discover drugs
or leads that have unexpected activities.
Streptomycin was founded by this method.

16. Methods of lead Identification
ii) Nonrandom screening:
 It is a modified form of random
screening. In this method, only such
compounds having similar structural
skeletons with that of lead, are tested.

17. Methods of lead Identification
iii) Drug metabolism studies :
 Structural modifications are done in
drug molecule by the enzymes to
increase its polarity.
:-sulfanilamide discovered by
metabolic study of prontosil.

18.  Molecules are chemically modified
and characterized in order to obtain
compounds with suitable properties to
become a drug.
 Leads are characterized with respect
to pharmacodynamic properties such
as efficacy and potency in vitro and in
vivo, physiochemical properties, and
toxicological aspects.

19. Methods of Lead Optimization
1. Identification of the active part
2. Functional group optimization.
3. Structure activity relationship studies.
4. Design of rigid analogs

20. Identification of the active part
• Any molecule consist of essential and non
essential parts.
• Essential part is important in governing the
pharmacodynamic.
• Nonessential part is important in governing
the pharmacokinetic.
• The relevant group on a molecule that interact
with a receptor are known as bioactive
functional group.

21. • By selecting the proper functional
group , one can govern the drug
distribution pattern and can avoid the
occuring side effects.
Functional group optimization

22. Structure activity relationship studies
• The physiological action of a molecule is a
function of its chemical constituent.
• This observation is the basis of
interpretation of activity in the terms of
the structural features of a drug molecule

23. TRADITIONAL
DRUG
DISCOVERY
v/s TARGET
IDENTIFICATION&
VALIDATION
LEAD
IDENTIFICATION
LEAD
OPTIMIZATION
TARGET
IDENTIFICATION&
VALIDATION
LEAD
IDENTIFICATION
LEAD
OPTIMIZATION
Genomic
s
Data/basi
c
Research
,
Assay on
Animal
In
vivo/vitro
HTS
In
vivo/vitro
Toxicity
assay (in
vivo/vitro)
Genomic
s ,
Proteomi
cs
&
Bioinformat
ics
In silico
structure
based
design
HTS
In
vivo/vitro
Toxicity
assay (in
vivo/vitro
)
NEW
STRATEGIES
IN DRUG
DISCOVERY

24. References…
…
 Shenliang Wang, and Young-Tae Chang ; Tools for
target identification and validation; Current Opinion
in Chemical Biology 2004, pg. no.371–377
 Selzer, P.M., Brutsche and Mullner, H. (2000)
Target-based drug discovery for the development of
novel antiinfectives. Int. J. Med. Microbiol., pg. no.
290, 191–201.
 Du GH. Evaluation and validation of drug targets.
Acta Pharmacol Sin 2004; pg.no. 1566.