This document discusses drug repositioning, which is the process of identifying new therapeutic uses for existing drugs. Drug repositioning can save both time and costs compared to new drug development, as the safety and toxicity of repositioned drugs are already understood. Strategies for repositioning include activity-based screening using in vitro and in vivo assays, as well as in silico computational screening. Several successful examples of repositioned drugs are provided, along with some drugs currently in clinical trials for new indications.

1. Drug Repositioning
FARIAH QAISER
Mphil 2nd Semester
Roll No. 02332213002

2. Contents
 Definition of Drug Repositioning
 Purposes & Benefits of Drug Repositioning
 Strategies and Approaches of Drug Repositioning
 Marketed Examples of Repositioning
 Drugs under Clinical Trials for Repositioning

3. Drug Repositioning
Introduction
The process of drug discovery involves many stages but can be categorized into
three stages namely:
 Lead identification
 Preclinical testing in animals
 Clinical trials in humans
In order to avoid such long term process of conventional drug discovery,
in drug development strategy is exploration of drug that have already been
approved for the treatment of other diseases and/or whose targets have already
been discovered.
“Drug repositioning can be defined as a process of identification of
new pharmacological indications from
old/existing/failed/investigational/already marketed/FDA approved
drug/pro-drug, and the application of the newly developed drugs to
the treatment of disease other than the drug’s intended therapeutic

4. Purpose of Drug Repositioning

5. Many pharmaceutical companies are working on the development of new
drugs, but the rate of gaining approval through clinical trials is very low
compared to the financial and time investment
In fact, it takes about 14 years to develop new drugs through de novo drug
discovery.
Despite prodigious increases in pharmaceutical R&D industry, productivity
has decreased in terms of the number of new drugs approved or the
number of original Investigational New Drug (IND) applications from
commercial sources.
In response, interest in repurposing clinically approved drugs
has increased.

6. Specifically, reduced development risk has been achieved because in
vitro/in vivo screening, toxicology, chemical optimization, and
formulation development have already been done and can be omitted.
Thus, pharmaceutical companies and researchers have started to
heavily invest in drug repositioning, which offers dramatic risk-
reward trade-off over de novo drug discovery.
Drug repositioning is safe for humans in preclinical models and, due
to only testing a drug’s effectiveness towards a specific disease,
benefits from a very small burden of failure.

8. Benefits of Drug Repositioning
1. Saving time:
The duration of the discovery phase for a repurposed drug is shorter as safety and
toxicology studies have already been assessed in the original indication.
2. Saving cost:
It costs approximately US $300 Million to bring a repurposed drug to market
representing a saving of about 85% compared to the US$ 2.6 Billion for a new drug
if the cost of failed projects is taken into account.
Drug Repositioning holds a higher reward with a lower risk

10. Strategies of Drug Repositioning

11. Approaches of Drug Repositioning
Activity based Approach In-silico based approach
Experimental (in vitro-in vivo) screening Computational (virtual) screening
Target-based and cell/organism-based
screening assay
Protein target-based screening
Requires no structural information of target
proteins
Requires structural information of target
proteins
Time and labor consuming Time and labor efficient
Lower rate of false positive hits during the
screening
Higher rate of false positive hits during the
screening

12. Examples of repositioned drugs and their
Indications

13. Drug Name Original Indication New Indication
Duloxetine Depression Chronic musculoskeletal pain
Minoxidil Hypertension Hair loss
Sildenafil Angina Erectile dysfunction,
pulmonary arterial
hypertension
Thalidomide Morning sickness (withdrawn) Leprosy
Amphotericin B Fungal Infection Leishmaniasis
Amantadine Influenza Parkinson’s Disease
Bromocriptine Parkinson’s Disease Diabetes Mellitus
Azathioprine Rheumatoid Arthritis Renal Transplant
Retinoic Acid Acne Promyelocytic Leukemia

14. Drugs under Clinical trials for Repositioning

15. Drug Original Indication New Indication Clinical Trial
Metformin Type II Diabetes Prostate Cancer Phase III Randomized
Studies
Exenatide Diabetes Type II
Incretin Mimetic
Parkinson’s Disease A larger phase 3,
placebo-controlled
and 96-week clinical
trial
Triumeq (dolutegravir
+ abacavir +
lamivudine)
Anti-retroviral drug
used in anti-HIV
therapy
Amyotrophic Lateral
Sclerosis (ALS)
Under clinical trials
Nelfinavir AIDS Multiple Cancers Under Clinical Trials