Drug Discovery

Drug discovery is a
process which aims
at identifying a
compound
therapeutically useful
in curing and treating
disease
Target identification Target validation

Target identification is process of Target validation is the process by

which the predicted molecular target
identifying the direct molecular
– for example protein or nucleic acid
target(protein, nucleic acid, or
– of a small molecule is verified.
small molecule). Target validation can include
Identifying the biological  of the knockdown or overexpression of the
disease and the potential targets presumed target. Tools for Target
Validation Antisense technologies si
for involvement ,is the first step in
RNA Antisense Oligonucleotides 15
the discovery of a medicine.

lead identification & optimization Product Characterization

When any new drug molecule shows a

1 Identification of Lead Once a target & a testing
promising therapeutic activity, then the
system has been chosen, the next is to find a “Lead
molecule is characterized by its size, shape,
Compound” which shows the desired
strength, weakness, use, toxicity, and
pharmaceutical activity.
biological activity. Early stages of
A lead compound is generally defined as a new
pharmacological studies are helpful to
chemical entity that could potentially be developed
characterize the mechanism of action of the
into a new drug by optimizing its beneficial effects
compound.
and minimizing its side effects.

2   Lead Optimization Molecules are chemically

modified and subsequently 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, pharmacokinetic
properties, and toxicological aspects.  Once
compounds with desirable in vitro profiles have
been identified, these are characterized using in
vivo models.

Preclinical Testing
Preclinical studies are conducted to define pharmacological and toxicological effects not
only prior to initiation of human studies but throughout clinical development.  Both in vitro
and in vivo studies can contribute to this characterization
The pre-clinical trials can be conducted in two ways: General pharmacology and Toxicology.
Pharmacology deals with the pharmacokinetic and pharmacodynamic parameters of drug.
Pharmacokinetic studies are very important to make known the safety and efficacy
parameters in terms of absorption, distribution, metabolism and excretion.

The Investigational New Drug

Process (IND) Clinical Research

Drug developers must file an Clinical trials are conducted in people

Investigational New Drug application to (volunteer)and intended to answer specific
FDA before commencement clinical questions about the safety and efficacy of
research.In the IND application, drugs, vaccines, other therapies, or new
developers must include: methods of using current treatments
• Preclinical and toxicity study data It generates data for discovering and
• Drug manufacturing information verifying the Clinical, pharmacological
• Clinical research protocols for studies to (including pharmacodynamic and
be conducted pharmacokinetic) and adverse effects with
• Previous clinical research data (if any) the objective of determining safety and
• Information about the investigator/ efficacy of the new drug
developer.

Phase 0 clinical trial Phase 1: Safety and dosage

Phase 0 clinical trials, developed in response

to the United States Food and Drug
Administration (FDA)'s recent exploratory
Investigational New Drug (IND) guidance, are
intended to expedite the clinical evaluation of
new molecular entities.Phase 0 trials besides
termed as human micro dose studies, they
have single sub-therapeutic doses given to 10
to 15 volunteers and give pharmacokinetic
data or help with imaging specific targets
without exerting pharmacological actions
First stage of testing in human subjects
• Designed to assess the safety, tolerability, PK and PD of
drug.
• 20-25 healthy volunteers 
The aim of a Phase I trial is to determine the maximum
tolerated dose (MTD) of the new treatment. •  Phase I trials
are the first tests of a drug with a lesser number of healthy
human volunteers. In most cases, 20 to 80 healthy
volunteers with the disease/condition participate in Phase.

Phase 3: Efficacy and

Phase 2: Efficacy and side effects adverse drug reactions
monitoring
Objectives
Objectives
Therapeutic confirmatory trials.
• Efficacy in patients (primary objective)
• Large scale, multicentre, Randomised, Controlled
• Safety issues (secondary objective)
trials .
• Optimum dose finding
• Target population: several 100’s to 3000 patients.
• Dose efficacy relationship
• Takes a long time: up to 5 years
• Therapeutic dose regimen
• To establish efficacy of the drug against existing
• Duration of therapy
therapy in larger number of patients, method of
• Frequency of administration
usage, & to collect safety data etc.
• Therapeutic window

Phase 4: Post-Market Drug

New Drug Application Safety Monitoring

A New Drug Application (NDA) expresses the Objectives 

full story of a drug molecule. Its purpose is to
verify that a drug is safe and effective for its
proposed use in the people studied. A drug
developer must include all about a drug
starting from preclinical data to Phase 3 trial
Done after drug has been marketed • Post Marketing
Surveillance (PMS).
No fixed duration / patient population
studies continue to collect data about effects in
various populations & side effects from long term use.

datain the NDA. Developers must include
reports on all studies, data, and analysis.
Detect the unknown/rare adverse drug reaction/s
Evaluation of over-dosage
Identifications of new indications
Dose refinement: Evaluation of new formulations,
dosages, durations of treatment 

Evaluation in different age groups / types of patients

Comparative Benefit-Risk assessment 

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