Unit 1

Question 1

What are the steps from Target to Pill?

Answer 1

9 Steps are involved

1. Target ID
2. Hit ID
3. Hit to Lead
4. Lead Opti
5. IND Enable
6. PI
7. PII
8. PIII
9. FDA filing
10. NDA filling

Question 2

What are the steps from Target to Pill?

Answer 2

9 Steps are involved

1. Target ID(Screening)
2. Hit ID
3. Hit to Lead
4. Lead Opti
5. IND Enable
6. Phase I
7. Phase II
8. Phase III
9. FDA filing
10. NDA filling

Question 3

What is causing the disease?

Answer 3

1. Infectious agents or Host Imbalance
   Molecular target leading to disease
   If bacteria: Find target not in host in bacteria itself
   If Host Imbalance: Find Target in host not in bacteria
   -Replace underactive protein-Insulin Underacting protein
   -Inhibit overacting protein- Kinase

Question 4

Target Identification

Answer 4

Target identification and characterization begins with identifying the function of a possible therapeutic target (gene/protein) and its role in the disease. Identification of the target is followed by characterization of the molecular mechanisms addressed by the target.

Question 5

Target Validation

Answer 5

Target Validation shows that a molecular target is directly involved in a disease process, and that modulation of the target is likely to have a therapeutic effect. The most important criteria for target validation is to take multi-validation approach

Question 6

Ways to identify a hit

Answer 6

1. Start with a natural substrate and make drug like
2. Start with someone else’s hit (Patent bust)
3. Design a denovo hit by structure based design
4. Screening (HTS or Fragment Methods)

Question 7

Drug Discovery Phases-What is a drug?

Answer 7

• Drugs are chemical or biological substances that have some kind of
physiological or biochemical effect on our bodies.
• They may be single compounds or a mixture of different compounds.
• Their effects are intended to be beneficial but can cause harmful side
effects in some people.
• All drugs interact with specific ‘targets’ in the body, with the aim of modifying their activity and often resulting in a therapeutic effect. For example, pain relief.

Question 8

Drug Discovery Phases-How is a drug developed?

Answer 8

The development of a new therapeutic drug is a complex, lengthy and
expensive process.
• It can take 10-15 years and over £500 million to develop a drug from an
initial concept, test its safety and effectiveness in humans and then get
it into the hospital market, this includes:
– 2-4 years of pre-clinical development
– 3-6 years of clinical development
– additional time for dealing with the regulatory authorities.

Question 9

Drug Discovery Phases-Drug discovery

Answer 9

The first stage of the drug development process is drug discovery.
• In the past, some drugs have been discovered by accident, for example:penicillin.
• Today, more systematic approaches are used, such as:
– high-throughput screening: which allows scientists to test thousands of potential targets with thousands of diverse chemical compounds to identify a new drug-target combination.
– rational drug design: which involves designing and synthesising compounds based on the known structure of a specific target molecule.
• While high-throughput screening may identify hundreds of potential lead components, many will be eliminated at the first round of testing.
During this round compounds are tested in cultured cells or animals to find out how effective they are and whether they have any toxic effects.
• Rational drug design develops fewer compounds compared to high-throughput screening. However, these compounds are very specific to the target and use computer-based modelling to achieve this specificity.

Question 10

Drug Discovery Phases-Pre-clinical development

Answer 10

• Pre-clinical testing is used to determine how best to develop the drug for its intended use.
• It aims to establish how drugs are absorbed and distributed in the body, and how they are broken down and removed from the body.
• If appropriate, promising drugs may be modified in an attempt to improve their properties in subtle ways in a process called lead optimisation.
• The results of pre-clinical testing are also used to determine how to best formulate the drug for its intended clinical use, for example whether it
would be most effective as a cream, a pill, an injection or a spray.
• The pre-clinical studies aim to whittle hundreds of compounds down to just a few useful candidate drugs.
• These few drugs will then be submitted to the appropriate regulatory authorities and, if accepted, the compound can be taken on to clinical development.

Question 11

Drug Discovery Phases-Clinical development

Answer 11

• This is divided into Phases 0, I, II, III and IV.
• Clinical development, also known as clinical trials, involves testing the drug on human volunteers to provide more information about its safety and effectiveness.
• By the end of the clinical development phase, most of the investigational new drugs will have been eliminated on the grounds of safety and effectiveness.
• Only one or two compounds will be submitted as a new drug application. In the UK, this is known as a market authorisation application.
• After a drug has been approved by the appropriate regulatory bodies, pharmaceutical companies have a short period where only they have the rights to market the drug (exclusivity) and before other companies can
market the same drug.
• This exclusivity period is used to regain the massive investment required to develop and launch the new drug.
• After full approval, drug companies must continue to test their drug and monitor feedback from healthcare professionals to ensure the safety and effectiveness of the drug.
• After launching a drug, new side effects or risk factors may be identified that had not been previously recorded. This is Phase IV of clinical development and is part of the continued monitoring of the effectiveness
of the drug in their target patients.

Question 12

The stages of drug discovery project

Answer 12

The stages of drug discovery project

1. 1 Choose a Target
2. 2 The Search
3. 3 High Throughput Screening
4. 4 Rational Drug Design
5. 5 Pharmacology
6. 6 Candidate is Chosen
7. 7 Toxicity Testing
8. 8 Phase I Clinical Trials
9. 9 Formulations/Bottling and Packaging
10. 10 Phase II Clinical Trials
11. 11 Phase III Clinical Trials
12. 12 Final Registration
13. 13 Conclusion

Question 13

The stages of drug discovery project-Choose a Target

Answer 13

The drug discovery process begins with understanding how a disease changes biological processes in the body, even if the exact cause isn’t known. Researchers hone in on the target, typically a protein that may be involved with this disease process. They then form a hypothesis that inhibiting or activating this protein will help treat the disease. Proteins are the most common drug targets because they play so many critical roles in the body, performing a variety of biological process from mounting an immune response to facilitating
nerve and hormone responses. A drug target can also be DNA or RNA. A good target must be responsive to small molecules or biologics.

Question 14

The stages of drug discovery project-The Search

Answer 14

They often begin by screening millions of these compounds for their ability to interact with the intended target. Of the millions screened, the candidate pool will be narrowed down to about 5,000 compounds and eventually to one or more “lead” compounds that will
continue to be optimized through safety and efficacy testing.

Question 15

The stages of drug discovery project-High Throughput Screening

Answer 15

Scientists can quickly test millions of compounds from the library to zero in
on a lead compound to advance to later stages of the drug discovery process.
It’s like launching millions of arrows at a target to see which ones land closet
to the bullseye. High-throughput screening is used at several stages in the
drug discovery process.

Question 16

The stages of drug discovery project-Rational Drug Design

Answer 16

In contrast to the trial-and-error process of HTS, this method begins with
knowledge of the shape of the protein target and then builds a compound
that optimally fits that target. Computer- aided 3-D modeling is used to
virtually screen and design these compounds. In order to do structure-based
design, scientists need to understand the form and function of a molecule. To
do this, they use high-tech tools such as crystallography—the study of the
arrangement of crystals to uncover the form and function of molecules—and
electron microscopes to determine the 3-D structure of a molecule and where
on the target protein the compound is binding.

Question 17

The stages of drug discovery project-Pharmacology

Answer 17

These stages together are critical for determining the right dose for the
medicine – the sweet spot between the minimum dose at which you see
a therapeutic effect and the maximum dose at which you don’t see toxicity.
Pharmacology encompasses pharmacokinetics and pharmacodynamics, that
is, what the body does to the drug and what the drug does to the body. For
example, does the drug has the properties to treat the disease? How it is

absorbed, distributed, metabolized and excreted? Pharmacology testing hap-
pens at multiple stages in the drug discovery process, in both preclinical and

clinical stages. This is another part of drug discovery where high-throughput
screening is useful.

Question 18

The stages of drug discovery project-Candidate is Chosen

Answer 18

It works! Months or years of study, hundreds or thousands of tests, have led to
a compound that can stop or reverse a disease that afflicts millions of people.
It’s exciting, but theory still needs to meet practice: It’s time to learn, through
a series of carefully managed clinical trials, if what works in the lab can be
turned into a viable treatment for real people.

Question 19

The stages of drug discovery project-Toxicity Testing

Answer 19

Scientists use several methods to nd a molecule that can serve as a potential
starting point of creating a new medicine. Often this process begins with the
company’s compound library, a collection of millions of chemical compounds
to screen against a biological target. They often begin by screening millions
of these compounds for their ability to interact with the intended target. Of
the millions screened, the candidate pool will be narrowed down to about
5,000 compounds and eventually to one or more ”lead compounds that will
continue to be optimized through safety and efficacy testing. A variety of
screening methods are used in this stage, which is a cycle of designing and
testing candidates for various properties.

Question 20

The stages of drug discovery project-Phase I Clinical Trials

Answer 20

The main goal of a Phase I trial is to test the safety of a medicine in healthy
volunteers at the predicted e ective dose. Additional pharmacological re
search happens here to determine what happens in the body when you take
a medicine–what the medicine does to the body and what the body does to
the medicine. To determine what is known as the maximum tolerated dose at
which it doesnt produce unacceptable side effects, the medicine is tested in
small groups of healthy volunteers, typically 20 to 100 people.

Question 21

The stages of drug discovery project-Formulations/Bottling and Packaging

Answer 21

The active ingredient is turned into a medicine that can be taken during the
next clinical phases. Important to this stage is optimizing the therapeutic
effect of a drug by delivering it in the proper way. For example, the rate at
which a drug needs to be delivered (slow release vs. quickly) determines the
inactive ingredients it’s packaged with. And the metabolic properties of the
drug also determine how it should be packaged — it needs to be delivered to
the bloodstream in a way that balances absorption, metabolism, and excretion.

Question 22

The stages of drug discovery project-Phase II Clinical Trials

Answer 22

Only now is the safety and efficacy of the drug ready to be tested in patients
with the disease or condition. In Phase II, the drug is tested for side effects
and to determine whether and how it helps the condition being studied in
up to several hundred people. In both Phase II and Phase III, the new drug
is compared to an existing drug, if available. Phase III, which includes 300
to 3,000 volunteers, is used to determine how the new drug may fit into the
treatment of the condition being studied.

Question 23

The stages of drug discovery project-Phase III Clinical Trials

Answer 23

Phase III, which includes 300 to 3,000 volunteers, is used to determine how
the new drug may fit into the treatment of the condition being studied. The
drug will also be tested on the people with co-morbidities.

Question 24

The stages of drug discovery project-Final Registration

Answer 24

Regulatory Affairs is involved in the entire process of drug development, in
order to make sure that the research plan for a potential medicine is in line
with what regulatory agencies like the U.S. Food and Drug Administration
(FDA) require. Regulatory Affairs is instrumental in the process of getting
the potential medicine ready for approval at the various stages of clinical
trials. For example, before Phase I clinical trials can begin, Regulatory A airs
must submit an Investigational New Drug (IND) application to the regulatory
agency, such as the FDA. After Phase III, Regulatory Affairs submits a New
Drug Application (NDA) to the regulatory agency. The NDA includes data on
the drug’s safety and efficacy in its proposed use, and on the risks and benefits
of using that drug. The NDA also includes data on a drug’s proposed labeling,
and on proposed manufacturing methods that are expected to preserve the
drugs strength, quality, and purity. Regulatory A airs also combines data into
a dossier for use in communicating the potential new medicine’s value for
reaching an unmet medical need.

Question 25

The stages of drug discovery project-Conclusion

Answer 25

A new treatment for an illness that might once have been thought
incurable. Success required weeks, months, and eventually years of persistent
work. It called on scientists, physicians, programmers, managers, investors,
salespeople, manufacturers, marketers, and the best kind of bureaucrats to
work together. It couldn’t have happened without hundreds of patients who
volunteered for trials. The path from idea to pharmacy shelf is long, and it’s
never a straight one. It doesn’t always reach the finish line. But when it does,
and thousands or millions of people live better, longer lives, there’s one fact
that no one involved doubts: It was all worth it.