The document discusses molecular targets used in drug development, which include cellular structures that can be visualized through molecular imaging, gene mutations, and protein levels associated with disease processes. It outlines the processes of target discovery, identification, validation, and various modeling techniques essential for understanding functional mechanisms and rational drug design. Additionally, the document highlights approaches for genetic manipulation and bioinformatics in identifying potential therapeutic targets.

1. Amjad Khan Afridi

2. MOLECULAR TARGET
Molecular targets are cellular or tissue structures that are
intended to be visualized by means of molecular imaging.
Different biological structures can potentially serve as
imaging targets.
 These Targets ranging from gene mutations, mRNA
levels, protein levels, DNA, RNA and enzyme activities.

3.  Those targets are basically associated with a particular disease
process and that could be addressed by a drug to produce a
desired therapeutic effect.
 The researchers have obtained samples from the National Cancer
Institute panel of 60 human tumor cell lines and measured a
variety of targets in these cell lines.
 Targets include gene mutations, mRNA levels, protein levels and
enzyme activities.
Cont…

4. TargetDiscovery
 Target discovery is the start of the drug development
pipeline, where the goal is to identify genes that can be
modulated to affect the clinical indicators and outcome
of specific diseases.
 High value target candidates can be defined as genes
that, when modified, affect disease progression without
having severe harmful effects on the physiology of the
organism.

5. Others MolecularTarget ofDrug
There are four main targets for drug action: like; receptors,
ion channels, enzymes and carrier molecules.
In each of these four cases, most drugs are effective because
they bind to particular target proteins.
Endogenous hormones and some drugs pass through the
cell membrane and attach to receptors in the cytoplasm.

6. The Target Identification & Characterization
 Target identification and characterization begins with
identifying the function of a possible therapeutic
target (gene/protein) and its role in the disease.
 A good target should be effective, safe, meet clinical
and commercial requirements and be "druggable".

7. Target Validation
 Target validation is the first step in discovering a
new drug and can typically take 2-6 months.
 A molecular target is directly involved in a
disease process, and that modulation of the target
is likely to have a therapeutic effect.

8. Development Models
 Molecular modelling is one of the fastest growing fields
in science.
 Actually, based on conceptual stage (to created concept
regarding to develop drug)
 It may vary from building and visualizing simple
molecules in three dimensions (3D) to performing
complex computer simulations on large proteins and
nanostructures.

9. Development Models
 Most currently used therapeutic drugs have an
enzyme or a membrane-bound receptor as site of
action.
 The sequencing of the human and other genomes has
provided a potential to identify many previously
unknown proteins that might serve as new drug
targets.

10. Development Models
 To study three-dimensional structures of
protein/biomolecule, it is critical for the
understanding of their functional mechanisms, and for
a rational drug design.
 Over the last decade atomic resolution crystal
structures of soluble proteins have been reported in a
rapidly increasing number, but the detailed three-
dimensional structures are still unknown for the
majority of membrane proteins since their membrane
association makes experimental structure
determinations complicated.

11. Development Models
Computerized modelling of protein structures, based
on experimentally determined structures of
homologue proteins, may be a useful methodological
alternative, especially for membrane proteins.

12. Approaches
 Data mining using bioinformatics — identifying,
selecting and listing potential disease targets
 Genetic association — genetic polymorphism and
connection with the disease
 Expression profile — changes in mRNA/protein
levels
 Pathway and phenotypic analysis — In vitro cell-
based mechanistic studies
 Functional screening — knockdown, knockout or
using target specific tools

13. Approaches
 Genetic manipulation of target genes (in vitro) —
knocking down the gene (shRNA, siRNA, miRNA),
knocking out the gene (CRISPR, ZFNs), knocking in
the gene (viral transfection of mutant genes)
 Antibodies — interacting to the target with high
affinity and blocking further interactions
 Chemical genomics — chemical approaches against
genome encoding protein

14. Thank You
26th October, 2021