Drug repositioning, also known as drug repurposing, refers to finding new uses for existing drugs outside their original therapeutic area. This approach can significantly reduce the time and costs associated with drug development. The document discusses various strategies for drug repositioning such as in silico screening and establishing drug-target-disease relationships from omics data. It provides examples of existing drugs that have been successfully repositioned for new indications, and strategies for repositioning existing drugs to treat COVID-19 more rapidly. Drug repositioning is an important approach that can accelerate the development of new treatments.

1. Drug Repositioning
VISHAKHA VIKRAM DESHMUKH
B PHARM VIII SEM
ROLL NO. 18
Y.B. Chavan College of Pharmacy
Dr. Rafiq Zakaria Marg, Rauza Bagh,
Aurangabad

2. Introduction
The process of drug discovery involves many stages but can be categorized into three stages
namely: lead identification followed by preclinical testing in animals and then clinical trials
in humans. In order to avoid such long term process of conventional drug discovery, reverse
engineering process is gaining importance. Another alternative 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 original/intended therapeutic use.

3. Synonym terms to Drug Repositioning
Drug repositioning: finding new uses outside the scope of the original medical indication
for existing drug or developing new indications for existing drug or biologics.
Drug repurposing: identification, developing and commercializing new uses for existing
or abandoned drugs.
Drug reprofiling: reducing the risk and associated with drug development with the
advantage that the drug has already undergone preclinical and clinical testing.
Drug reformulating: finding ways to modify a formulation to allow a drug to enter a new
market.
Drug rediscovery: investigating new uses for currently prescribe drugs.

4. Need 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.
3. Other reasons:
a. A significant number of drugs are repurposed for rare diseases which attracts many
developers due to the incentives.
b. FDA and EMA offend provide incentives in such situations.
c. In addition to a lower cost of clinical trials and a shorter development time, drug
repurposing is associated with a higher success rate from Phase II to launch

5. Drug repositioning Approaches and
Resources
The concept of re-profiling or repurposing a drug is deep-rooted on the grounds of poly-
pharmacology that reveals the small print on on-target and off-target proteins through which
a drug exhibits both anticipated and untoward effects.
Repurposing of a drug is carried out in the following steps:
1. In silico approach
2. Experimental approach
All the technologies like genomics, proteomics, transcriptomics, and databases which include
drug omics data, disease omics data are interconnected in designing the strategy for a
proposal of a drug to be repurposed.

6.  Drug Repurposing starts with:
1. Collection of raw data related to disease-drug-targets
2. Establishment of drug-target-disease relationship
3. Support of potential evidence
4. in silico screening techniques
5. Generation of proof of concept
6. Generation of experimental evidence
7. Further the shortlisted compounds pass through clinical trials
8. FDA approval
9. Successful repositioning of drug
 Computational Techniques in Drug Repurposing
Computational
techniques
Signature Based
Target Based
Drug Based
Literature Based

7. Challenges and Opportunities
Although much progress in drug repurposing has been made in recent years, regulatory
approval is the only aim for a successfully repurposed drug. Many challenges to meeting this
goal can be foreseen, from the developmental phase all the way to regulatory approval.
1. Optimization of inclusion and exclusion criteria in selection of target population
2. Achievement within timeline
3. Requirement for robust evidence
4. Lack of funding to commercialize the product
5. Clinical trial feasibility for rare diseases
6. Technical challenges to repurposing drugs
7. Novelty in repurposing

8. Few latest Drug Repositioning examples
Drug Original indication New indication
Albuterol Exercise induced bronchospasm Prevention of paralysis due to spinal cord
injury
Bupropion Depression Smoking cessation
Digitoxin Cardiac arrhythmias & heart failure Treatment of ovarian cancer.
Eflornithine African trypanosomiasis Pneumocystis carinii pneumonia in AIDS
patients
Finasteride Benign prostatic hyperplasia Hair loss
Galantamine Polio, paralysis & anaesthesia Alzheimer’s disease
Celecoxib Osteoarthritis & adult rheumatoid arthritis Familial adenomatous polyposis
Infliximab Crohn’s disease Juvenile rheumatoid arthritis
Heparin Anticoagulant & Venous thrombosis Cystic fibrosis
Ketoconazole Systemic fungal infection Nephrotoxicity

9. Drug Original Indication New Indication
Leflunomide Arthritis Myeloma
Nitroprusside Acute congestive heart failure Cerebral vasospasm
Omega-3(n-3) polyunsaturated fatty
acids
High triglyceride level reduction IgA nephropathy
Phentolamine Dermal necrosis Autism
Ropinirole Hypertension Restless leg syndrome
Sodium thiosulfate Cyanide poisoning Platinum-induced ototoxicity in
paediatric patients
Topiramate Epilepsy Obesity & irritable bowel syndrome
Zidovudine Cancer AIDS
Artemizole Allergies Malaria
Amphotericin-B Fungal infection Leishmaniasis
Sildenafil Erectile dysfunction African sleeping sickness
Metformin Type-2 diabetics PCOS
Minoxidil Hypertension Hair growth

10. Drug Repositioning strategies for COVID-19
COVID-19 has now been declared a pandemic and new treatments are urgently needed as we
enter a phase beyond containment. Developing new drugs from scratch may be a lengthy
process, thus impractical to face the immediate global challenge.
Here we take a snapshot look at the strategy of drug repurposing that promises to identify
antiviral agents for the novel coronavirus disease in a time-critical fashion. Also, a
perspective that antiviral combinations with a ‘double hit effect’ may offer the best chance of
success and clinical translatability.
1. Repurposing of existing antivirals
2. BSAA combination therapy

11. Conclusion
Drug discovery and development is a costly, complex, and time-consuming process, often
taking 14 to 20 years and $1 billion-plus in Research and Development costs, with no
guarantee of success. The use of drug repurposing such time- consuming and costly process
that can be easily overcome.
Apart from saving time this technique of drug use also favors the development of research
for academics, development of an academic institute-industry relationship.
The most important advantage would be to the patient as the drug availability for new
disease would be quicker, relieving him of disease-related suffering.

12. Thank you!