Module 1

Question 1

A process which is intended to identify a small synthetic molecule or a large bio-molecule for comprehensive evaluation as a potential drug candidate

Answer 1

Drug Discovery

Question 2

researchers discover new
drugs through:

Answer 2

• N-new insights into a disease process
• M-many tests of molecular compounds
• E-existing treatments that have unanticipated effects.
• N-new technologies

Question 3

The _____ are
further optimized to improve
their efficacy and
pharmacokinetics before
they advance towards drug
development

Answer 3

lead compounds

Question 4

The process of bringing a new pharmaceutical drug to the
market once a lead compound has been identified
through the process of drug discovery.

Answer 4

DRUG DEVELOPMENT

Question 5

It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.

Answer 5

DRUG DEVELOPMENT

Question 6

Once researchers identify a promising compound for development, they conduct experiments to gather information
on:

Answer 6

• How it is absorbed, distributed, metabolized, and excreted.
• Its potential benefits and mechanisms of action.
• The best dosage.
•The best way to give the drug (such as by mouth or injection).
• Side effects or adverse events that can often be referred to as toxicity.
• How it affects different groups of people (such as by gender, race, or ethnicity) differently.
• How it interacts with other drugs and treatments.
• Its effectiveness as compared with similar drugs.

Question 7

Before testing a drug in people,
researchers must find out whether it has the potential to cause serious
harm, also called toxicity.

Answer 7

PRECLINICAL
DEVELOPMENT

Question 8

The two types of preclinical research are:

Answer 8

In Vivo
In Vitro

Question 9

In preclinical development, toxicological and safety pharmacology studies of the candidate are conducted in order to
establish the ________ in animals and determine the adverse effect
potential of the drug-in-development.

Answer 9

maximum safe concentrations

Question 10

FDA requires researchers to use __________, defined in medical product development regulations, for preclinical laboratory studies.

minimum basic requirements for:
• study conduct
• personnel
• facilities
• equipment
• written protocols
• operating procedures
• study reports

Answer 10

Good laboratory practices
(GLP)

Question 11

The GLP regulations are found in ________: Good Laboratory Practice for Nonclinical Laboratory
Studies.

Answer 11

21 Code of Federal Regulations (CFR) Part 58.1:

Question 12

Studies are conducted
to finalize ___________ required for
manufacturing the candidate drug as well as __________

Answer 12

Cost-effective processes…deciding on its best formulation

Question 13

The trigger to initiate a drug discovery program is a medical condition whose treatment is not satisfactorily addressed by currently available treatment modalities.

Answer 13

IDENTIFICATION OF UNMET MEDICAL NEED

Question 14

The trigger to initiate a drug discovery program is a medical condition whose treatment is not satisfactorily addressed by currently available treatment modalities.

Answer 14

IDENTIFICATION OF UNMET
MEDICAL NEED

Question 15

Biologically active compounds, whether they be a small synthetic molecule or a large molecular weight antibody, elicit their activity and thereby a measurable clinical effect by interacting with a naturally existing molecular structure

Answer 15

TARGET IDENTIFICATION

Question 16

Examples of target molecules:

Answer 16

• Enzymes
• Receptors
• Metabolites
• Substrates
• Ion channels
• Transport proteins
• DNA, RNA, and ribosomes

Question 17

Have been scientifically proven to have well-defined physiological and pathophysiological roles fall.

Answer 17

Established targets

Question 18

Newly discovered ones whose role is turning out to be clearer with advancing research

Answer 18

Novel Targets

Question 19

A potential drug target needs to undergo the process of validation where in its function in a disease state is ascertained

Answer 19

TARGET VALIDATION

Question 20

Next step is identification of ‘hits’, which in a broad
sense may be defined as compounds that elicit the
desired activity in a screening assay

5 examples:
• High throughout screening (HTS)
method
• Fragment-based screening
• Focused screening strategy
• Phenotypic screening

Answer 20

HIT IDENTIFICATION & DEVELOPMENT OF ASSAYS

Question 21

The identified hits are subjected to confirmatory evaluation using the same assay conditions which were employed during hit identification

It is imperative to ascertain that the activity is linked to the anticipated mechanism and is not due to artifacts.

Answer 21

CONFIRMATION OF HITS

Question 22

Procedure of detecting false
positives is to employ a counter-
screening assay in which hits are
evaluated for their activity
against an alternative member of
the target family under identical
assay conditions and if the hit
demonstrates similar activity
then it is most likely a false
positive.

Answer 22

NA

Question 23

Also referred to as hit to lead phase, involves optimization of the identified hits from a diverse series to generate lead compounds

Answer 23

LEAD GENERATION

Question 24

In this stage, compounds synthesis is initiated by medicinal chemists by using various approaches like conventional organic chemistry and combinatorial chemistry.

Screening flow for lead identification comprises of in vitro evaluation in primary/cell-free assays as well as specificity of the compounds for the
target.

Further, the activity of compounds is
also evaluated in known animal orthologs of the target as
the compounds have to be evaluated for
their efficacy in animal models.

Answer 24

LEAD GENERATION

Question 25

In addition, physicochemical properties of representative
compounds from the series being explored are also studied to confirm drug-likeness of the compounds.
As the most preferred route for administration of the drug is oral, the new chemical entity in development
should observe the Lipinski rule of 5 which asserts that a compound is more likely to be membrane
permeable and absorbed by the body if it matches the following criteria

Answer 25

LEAD GENERATION

Question 26

• Molecular mass:
• Its logP, lipophilicity:
• # of H-bond donors:
• # of H-bond acceptors

Answer 26

<500 daltons
< 5
donors is < 5
acceptors is < 10

Question 27

The goal of _______ is to generate preclinical development candidates by improving the shortcomings of
the lead structure by chemical modifications.

Generally, the aim is to enhance the physicochemical and ADME
properties and minimize the toxicity liabilities so that a
potentially safe compound with favorable pharmacokinetics is
identified.

Answer 27

LEAD OPTIMIZATION

Question 28

Once a preclinical drug candidate is selected, the drug development
process begins.

The drug is progressed through various studies designed to support
its approval by the regulatory bodies to move the candidate into clinical (human) study by submission of an Investigational New Drug (IND) application

Answer 28

PRECLINICAL DRUG DEVELOPMENT

Question 29

CRITERIAS TO SELECT A CLINICAL
CANDIDATE:

Answer 29

● Chemical properties
● Physicochemical properties
● Pharmacological properties
● Pharmacokinetic properties
● Safety and toxicity potential

Question 30

If the IND is approved, ________ begins.

Answer 30

Clinical Drug Development:

Question 31

A request from a clinical study sponsor to obtain authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans.

Answer 31

Investigational New Drug Application (IND)

Question 32

Testing on animals for toxicity.

INVESTIGATIONAL NEW DRUG APPLICATION

Describes the manufacturer’s plans for testing the drug in clinical trials.

If approved by FDA, the manufacturer becomes the sponsor of an “existing IND.”

Answer 32

PRE-CLINICAL

Question 33

Clinical trials test for safety and dosing ranges.

No. of patients: 20 to 80
Approximately 63.2% moved to phase II

Answer 33

Phase I

Question 34

Clinical trials test for efficacy in the patients that the drug is intended
to treat.

No. of patients: a few dozen to hundreds
Approximately 30.7% moved to phase lll

Answer 34

Phase II

Question 35

Clinical trials test for efficacy in the patients that the drug is intended to treat.

No. of patients: hundreds to thousands
Approximately 58.1% moved to the new drug application process

Answer 35

Phase III

Question 36

Once the drug has successfully completed the phase IlI trials, the manufacturer generally submits a new drug application to FDA.

Approximately 85.3% are approved

Answer 36

New drug application review

Question 37

FDA either approves or denies approval for the drug or biologic for marketing and sales in the U.S.

Answer 37

FDA approval results