Drug repurposing is the process of applying already-approved drugs and compounds to treat a different disease. Also synonymously called drug repositioning; however, there is a difference. Identifying, developing, and commercializing new uses for existing or abandoned drugs Finding new uses outside the scope of the original medical indication for existing drugs or developing new indications for existing drugs or biologics

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PRESENTED BY:
RIYA RAJESH GAGNANI
DEPARTMENT OF PHARMACOLOGY
CENTRAL UNIVERSITY OF PUNJAB

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3.  DRUG REPURPOSING
 RELATED TERMS
 HISTORY
 OBJECTIVE AND NEED
 STRATEGIES OF DRUG REPURPOSING
 METHODOLOGIES AND STEPS
 SUCCESSFUL REPURPOSING
 UNSUCCESSFUL REPURPOSING
 FUTURE ADVANCEMENT
 ADVANTAGES AND BARRIERS
 REFERENCES
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4.  Drug Repurposing is the process of application of an existing therapeutic
drug to a new diseases indication.
Or
 It is the process of application of already approved drugs and
compounds to treat a different disease.
 Also synonymously called Drug Repositioning however there is
difference.
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5. DRUG REPOSITIONING
• Finding new uses outside the scope of the original medical indication for existing drugs or
developing new indications for existing drugs or biologics
DRUG REPURPOSING
• Identifying, developing, and commercializing new uses for existing or abandoned drugs
DRUG REPROFILING
• Reducing the risks and costs associated with drug development with the advantage that the
drug has already undergone preclinical and clinical testing
DRUG REDISCOVERY
• Investigating new uses for currently prescribed drugs
THERAPEUTIC SWITCHING
• Opening up new possibilities for old medicines that were not appreciated at the time of original
discovery and can be made therapeutically different through new formulations
INDICATION SWITCHING
• Exploiting established drugs that have already been approved for treatment
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6. Initially, people were unaware of this term, although this method was practiced
in the late 1990s with the repositioning of thalidomide. The first example of
drug repositioning was an accidental discovery in 1920s.
The oldest example of Repurposing is without doubt aspirin. Intially marketed
by bayer in 1899 as an analgesic, aspirin was 1st repositioned in 1980s, at low
dose only, as an antiplatelet aggregation drug.
In mid 2000s sildenafil for angina repositioned to Erectile dysfunction and
thalidomide for morning sickness was repositioned to multiple myeloma. The
success created a big interest in repurposing which resulted in the formation of
many repurposing focused startup companies
According to one of the studies in recent years, more than 30% of the US Food
and Drug Administration (FDA)-approved drugs and vaccines have undergone
the drug repurposing process
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8. The objective of
drug
repurposing was
assumed to be to
identify or
discover new
targets for a
drug marketed
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Drug development can be time
consuming and expensive. Recent
estimates suggests that, on average ,
it takes 10 years and at least $ 1
billion to bring a drug to market
Moreover, investment in drug
development has been gradually
increasing, as reported by
Pharmaceutical Research and
Manufacturers of America (PhRMA)
So pharma companies have become
increasingly interested in finding new
uses for existing drugs- a process
referred to as drug repurposing or
repositioning

10. There are two main strategies of Drug Repurposing viz.,
 on-target
 off-target
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11. ON TARGET DRUG REPURPOSING
In on-target DR, the known pharmacological mechanism of a drug
molecule is applied to a new therapeutic indication. In this strategy,
the biological target of the drug molecule is same, but the disease is
different.
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OFF TARGET DRUG REPURPOSING
In the off-target profile, the pharmacological mechanism is
unknown. Drugs and drugs candidates act on new targets, out of the
original scope, for new therapeutic indications. Therefore, both the
targets and the indications are new.

12. METHODOLOGIES AND STEPS INVOLVED
TRADITIONAL DRUG DISCOVERY VS DRUG
REPURPOSING
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DRUG
REPURPOSING
(3-8 YEARS)
TRADITIONAL DRUG
DISCOVERY
(19-17 years)

13. Drug repurposing starts with collection of raw data related to disease-drug-targets
Followed by establishment of drug-target-disease relationship.
With an extensive support of potential evidence
and in silico screening techniques
proof of concept is generate which is then experimentally proved
Further the shortlisted compounds pass through clinical trials
for the new indication and enter the market with FDA labelling
FDA approval
Successful repurposing of drug
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Drug name Original target Original indication New target New indication
Thalidomide Inhibition of TNF‐α Anti-emetic Inhibition of cancer
cells
Multiple myeloma
Aspirin COX-1 inhibitor Anti-platelet COX-2 inhibitor Anti-cancer and
Analgesic effect
Carvedilol Autophagy Inducer Anti-inflammatory Autophagy Suppresser
and promoted
Apoptosis
Acute myocardial
infarction
Sildenafil Inhibiting
Phosphodiesterase
type‐5
Vasodilation Inhibiting
Phosphodiesterase
type‐5
(at low dose)
Pulmonary arterial
hypertension
Dimethyl
Fumarate
NRF2‐dependent
antioxidative genes
Psoriasis Enhance nuclear factor
erythroid 2 related
factor 2 (Nrf2)
transcriptional pathway
(high dose)
Multiple sclerosis
Minoxidil Adenosine 5'-
triphosphate-
sensitive potassium
channel opener
Antihypertensive
vasodilator
Hyperpolarization of
cell membranes
Androgenic alopecia
and alopecia areata
Amantadine Blocks the M2
viroporin channel
Antiviral activity
toward RNA viruses
Variably influences
different
neurotransmitter
systems
Neurological drug
Zidovudine Blocking nucleotide
synthesis
Anticancer Inhibited the
murine leukemia
virus (MLV)
Anticancer

15.  It is well known that the WHO banned thalidomide in 1962 due to its teratogenicity,
mainly through its use as an antiemetic for pregnant women.
 In 1964 Dr Jacob Sheskin demonstrate its dramatic efficacy against erythema
nodosum leprosum, by inhibiting the synthesis of the proinflammatory cytokine
TNF‐α.
 Thalidomide was repositioned for a second time in the field of oncology, by its
antiangiogenic activity, responsible for the arrested limb development (phocomelia) .
Due to its potential use to block or destroy blood vessels supplying malignant tumours,
in 2006 in its second repositioning as a first‐line treatment for multiple myeloma.
 This example illustrates how even drugs with an exceptionally poor toxicity profile can
be repositioned if the new indication is a rare disease
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• The oldest example of drug
repositioning is without doubt
acetylsalicylic acid.
• It shows at low doses only, as an
antiplatelet aggregation drug.
• It is widely used second indication to
prevent cardiovascular events.
analgesic and anti‐inflammatory effects
inhibition of COX‐2, in particular vascular COX‐2, which is involved in the synthesis of PGs that generate
pain and inhibit platelet aggregation
Prevent many cancers particularly colorectal cancer
protective effect against cancer after daily administration for at least 5years, by COX‐2 inhibition, thus
blocking the anti apoptotic effect of COX‐2 in malignant cells and promoting their apoptotic death
Inhibit Platelet aggregation by
inhibiting platelet COX‐1, responsible for the formation of the PGs precursor of thromboxane A2, a
potent stimulator of platelet aggregation
Low doses
aspirin has
partial
selectivity for
COX‐1 and
exerts its
antiplatelet
aggregation
effect,
At higher doses
is circumvented
by concomitant
COX‐2 inhibition

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Potential indications and mechanisms of carvedilol
The effect of carvedilol on autophagy. In liver
fibrosis, carvedilol suppressed autophagy and
promoted apoptosis, while it was repurposed
as an autophagy inducer with beneficial effects
on inflammatory diseases and after acute
myocardial infarction.

18.  Sildenafil was initially investigated by Pfizer in
1985 as a potential antihypertensive drug, shown to
produce vasodilation and to inhibit platelet
aggregation by inhibiting phosphodiesterase type‐5
(PDE5), the enzyme that degrades cGMP. Due to
its these properties, the focus was shifted onto its
potential in the treatment for angina.
 Sildenafil only produces an erection in the presence
of sexual stimulation, leading to the release of nitric
oxide (NO), which in turn leads to cGMP
production.
 This physiological effect led Pfizer to market
sildenafil in 1998 for erectile dysfunction, under the
brand name Viagra.
 Sildenafil was subsequently repositioned for a
second time, to treat pulmonary arterial
hypertension, at one‐fifth of the dose used in
erectile dysfunction.
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19.  Dimethyl fumarate is commonly used to treat psoriasis, under the brand name
Fumaderm®.
 Dimethyl fumarate’s anti‐inflammatory activity was mediated by increased
expression of NRF2‐dependent antioxidative genes used to treat relapsing forms
of multiple sclerosis (MS),at higher doses, act centrally by enhancing the
nuclear factor erythroid 2 related factor 2 (Nrf2) transcriptional pathway,
which regulates enzymes to counter act oxidative stress under the brand name
Tecfidera®.
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20.  Minoxidil is a medication used for the treatment of high blood pressure and pattern
hair loss. It is an antihypertensive vasodilator.
 When patients taking the antihypertensive agent minoxidil in clinical trials in the late
1960s started getting a bit hairy. Then a US based pharmaceutical company (Upjohn)
that made the drug — dismissed it as a harmless side effect.
 Used in androgenic alopecia and alopecia areata
 Minoxidil is an adenosine 5'-triphosphate- sensitive potassium channel opener,
causing hyperpolarization of cell membranes.
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21.  It effectively blocks the M2 viroporin
channel of the influenza A virus, display
antiviral activity toward RNA viruses other
than influenza A, such as Chikungunya
virus.
 In 1966 it was the first antiviral approved
by USFDA for prophylaxis against
influenza A ,specifically the subtype H5N1
known of its high case fatality rate but soon
after that influenza viruses developed
resistance to these drugs and amantadine is
no longer recommended.
 Currently amantadine is used mainly as
a neurological drug, for Parkinson’s
disease, and is also used off-label in
traumatic brain injury (TBI), multiple
sclerosis, etc. Amantadine displays good
penetrance to CNS and variably influences
different neurotransmitter systems
(dopaminergic, adrenergic, glutamatergic)
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22.  The first FDA approved anti-HIV medication,
zidovudine, was initially developed as an anti-
cancer medicine.
 Several scientists demonstrated that the molecules
that were blocking the nucleotide synthesis were
not only proven to be used as anti-cancer drugs
but also potent antibacterial as well as antiviral
drugs.
 These discoveries eventually led to the
development of zidovudine (AZT) by Horwitz in
1964 as a potent anticancer agent.
 A decade later, Ostertag et al., demonstrated that
zidovudine specifically inhibited the murine
leukemia virus (MLV) by blocking the virus
life cycle at a very early stage
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23.  Trastuzumab is a Monoclonal antibody
against the extracellular domain of the
HER2 receptor
 Trastuzumab (Herceptin) and Pertuzumab
(Perjeta) are given as neoadjuvant therapy
and only Trastuzumab is continued post-
surgery
 It Reduces cell growth and enzyme helps
body in using Herceptin.
 It is currently the only FDA-approved
therapeutic antibody for HER2-positive
breast cancer. That targeting
of HER overexpression
 Side effects are body pain, chills, cough,
diarrhea, fatigue, fever, headache and
heart problems.
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Drug name Original target Original
indication
New target New indication
Bevacizumab VEGF Multiple cancers Unchanged Failed clinical trials
for gastric cancer
Buproprion Unknown Depression Synergistic
inhibition of
appetite and energy
expenditure
Obesity(rejected by
FDA due to adverse
effects
Naltrexone Opioid receptors Opioid addiction Synergistic
inhibition of
appetite and energy
expenditure
Obesity(rejected by
FDA due to adverse
effects
Naltrexone Unknown Alcohol
dependence
Synergistic
inhibition of
appetite and energy
expenditure
Obesity(rejected by
FDA due to adverse
effects
Sunitinib Multiple kinases Renal cell
carcinoma
Multiple kinases Failed clinical trials
for multiple cancer

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27.  http://drugrepurposing.info/
 Rudrapal, M., J. Khairnar, S., & G. Jadhav, A. (2020). Drug Repurposing (DR): An Emerging Approach in
Drug Discovery. Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications. doi:
10.5772/intechopen.93193
 Trinh L. Doan, Michael Pollastri, Michael A. Walters, Gunda I. Georg,Chapter 23 - The Future of Drug
Repositioning: Old Drugs, New Opportunities,Editor(s): John E. Macor,Annual Reports in Medicinal
Chemistry,Academic Press,Volume 46,2011,Pages 385-401
 https://pharmaceutical-journal.com/article/news/how-minoxidil-was-transformed-from-an-antihypertensive-
to-hair-loss-drug
 https://en.wikipedia.org/wiki/Minoxidil#External_links
 Cantrell MS, Soto-Avellaneda A, Wall JD, Ajeti AD, Morrison BE, Warner LR, McDougal OM. Repurposing
Drugs to Treat Heart and Brain Illness. Pharmaceuticals (Basel). 2021 Jun 16;14(6):573. doi:
10.3390/ph14060573. PMID: 34208502; PMCID: PMC8235459.
 Jean-Pierre Jourdan, Ronan Bureau, Christophe Rochais, Patrick Dallemagne, Drug repositioning: a brief
overview, Journal of Pharmacy and Pharmacology, Volume 72, Issue 9, September 2020, Pages 1145–
1151, https://doi.org/10.1111/jphp.13273
 Trivedi J, Mohan M, ByraredSN. Drug Repurposing Approaches to Combating Viral Infections. Journal of
Clinical Medicine. 2020; 9(11):3777. https://doi.org/10.3390/jcm9113777.
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