Drug Reprofiling in the Age of Necessity: A Strategic-Clinical Synthesis for Therapeutic Clinical Outcome

Dr. Sinchu Yesudanam, Anshu Shyjin, M. Muhammed Aslam,

doi:10.5281/zenodo.16881340

Review Paper | Open Access
Volume 03 | Issue 08 | Article Id IJPS/250308166

Drug Reprofiling in the Age of Necessity: A Strategic-Clinical Synthesis for Therapeutic Clinical Outcome
Dr. Sinchu Yesudanam* Anshu Shyjin M. Muhammed Aslam
Mar Dioscorus College of Pharmacy.

Abstract

Drug reprofiling, also referred to as drug repurposing or repositioning, finds new therapeutic applications for drugs that are already on the market or have already failed. It provides quicker, less expensive, and less dangerous alternatives to traditional drug discovery. In in addition to addressing unmet medical needs in a variety of fields, such as infectious, neurodegenerative, oncologic, cardiovascular, metabolic, autoimmune, parasitic, and rare diseases, this strategy makes use of established safety and pharmacokinetic profiles to shorten development timelines and costs. Phenotypic and target-based approaches as well as computational methods like molecular docking are examples of strategies. Its effects during the COVID-19 pandemic and in chronic conditions where innovation is desperately needed are demonstrated by case studies. Drug reprofiling enhances drug lifecycles, speeds up personalised medicine, and supports global health initiatives by integrating into research pipelines and regulatory frameworks.

Keywords

Drug Reprofiling, drug repurposing, therapeutic innovation, repositioning, computational methods, phenotypic screening, molecular docking, COVID-19, rare diseases, personalized medicine

Introduction

Drug reprofiling, also known as drug repurposing or drug repositioning, is an emerging strategy in pharmaceutical research that focuses on identifying new therapeutic uses for existing or previously failed drugs⁽¹⁾. Unlike traditional drug discovery—which involves de novo synthesis, extensive preclinical studies, and time-consuming clinical trials—drug reprofiling offers a faster, cost-effective, and lower-risk approach by utilizing the known pharmacological and safety profiles of approved or investigational drugs⁽²⁾. The process of developing a new drug from scratch can take over 10–15 years and cost billions of dollars, with a high rate of failure, especially in the later stages of clinical trials⁽³⁾. Drug reprofiling circumvents many of these challenges by capitalizing on existing data, thereby significantly reducing development time and financial burden⁽⁴⁾. It is particularly valuable in addressing urgent healthcare needs, such as emerging infectious diseases, rare diseases, and cancers, where treatment options are limited or non-existent⁽⁵⁾. Numerous medications that have been repurposed have shown impressive results⁽⁶⁾. For example, thalidomide, which was once discontinued because of its teratogenic effects, has been successfully repurposed for the treatment of leprosy sequelae and multiple myeloma⁽⁷⁾. Another prominent example is sildenafil, which was first created to treat angina but was later used to treat pulmonary hypertension and erectile dysfunction⁽⁸⁾. Advancements in computational biology, bioinformatics, and artificial intelligence have revolutionized drug reprofiling⁽⁹⁾. In silico methods, molecular docking, network pharmacology, and machine learning now enable the rapid screening of large drug libraries against diverse disease targets⁽¹⁰⁾. These technologies facilitate the identification of novel drug-disease relationships and support the rationale for clinical repurposing studies⁽¹¹⁾. In the current pharmaceutical landscape, drug reprofiling not only enhances the lifecycle of existing drugs but also contributes to personalized medicine and global health initiatives⁽¹²⁾. Its integration into regulatory frameworks and drug development pipelines signifies a paradigm shift towards more efficient and sustainable therapeutic innovation⁽¹³⁾.

1.2 Stages of Drug Reprofiling Without AI Involvement

Drug reprofiling, also known as drug repositioning, refers to the strategy of identifying new therapeutic applications for existing or previously studied drugs⁽¹⁴⁾. While modern approaches often involve artificial intelligence and machine learning, traditional reprofiling techniques rely on well-established experimental methods, clinical observations, literature surveys, and conventional data analysis⁽¹⁵⁾. These methods are still widely used and continue to contribute significantly to drug discovery⁽¹⁶⁾. The following are the major stages of drug reprofiling without the involvement of AI:

1.2.1 Selection and literature review

Finding appropriate medication candidates for reprofiling is the initial step⁽¹⁷⁾. Frequently taken into consideration are medications that have already received approval, been withdrawn for non-safety reasons, or been put on hold because of ineffectiveness⁽¹⁸⁾. The pharmacological characteristics, safety profiles, and past clinical results of these medications are evaluated using literature reviews, regulatory documents, and clinical trial databases⁽¹⁹⁾. Drugs with off-target effects or unexpected therapeutic responses documented in previous trials or case studies receive special attention⁽²⁰⁾.

1.2.2 Target identification through experimental and literature-based approaches

Target identification is done manually by looking through the available pharmacological data and experimental trials when AI technologies are not available. Researchers look into potential secondary targets based on published data on the drug's mechanisms of action, known biochemical interactions, and structural similarities with other medications. Physiological effects noted, Scientific journals, pharmacology textbooks, biochemical assays, and route analysis from experimental research are typically the sources of these insights ⁽²¹⁾.

1.2.3 Disease Association Based on Clinical and Experimental Evidence

Linking the medication to illnesses where these targets are implicated comes next, after potential new targets have been identified. This procedure depends on a thorough comprehension of clinical pathology, illness causes, and the body of available literature. A medication with anti-inflammatory properties, for example, may be taken into consideration for disorders like arthritis, inflammatory bowel disease, or neuroinflammatory diseases. At this point, observational research, clinical case reports, and experimental illness models are crucial resources^(22,23).

1.2.4 Preclinical evaluation

Through laboratory based, the preclinical stage confirms the drug's potential in the novel indication. These consist of:

In vitro experiments: Drug testing on specific disease-relevant cell lines to evaluate cellular effects, cytotoxicity, and biomarker expression⁽²⁴⁾.
In vivo studies: Animal models are used to assess pharmacological activity, dosing, and disease outcomes⁽²⁵⁾.

These studies help determine whether the drug demonstrates sufficient efficacy in the new therapeutic context before progressing to human trials.

1.2.5 Clinical trials for the new indication

The medication moves on to clinical investigation if preclinical findings show promise. Phase I trials may be skipped in favor of Phase II or III trials, which concentrate on efficacy and the best dosage in the novel therapeutic area, because the safety of the medicine has already been demonstrated. These experiments could be carried out as

Investigator-initiated trials

Randomized controlled studies
Off-label use assessments (in some regulatory environments)

Trial design and ethical approvals are crucial in this stage to ensure robust and reproducible results⁽²⁶⁾.

1.2.6 Regulatory approval

Following successful clinical trials, a submission is made to the respective drug regulatory authority for approval of the drug’s new indication ⁽²⁷⁾. Depending on the jurisdiction and nature of the change, a Supplemental New Drug Application (sNDA) or a formal request for label expansion is submitted⁽²⁸⁾. Regulatory agencies like the FDA, EMA, or CDSCO evaluate the submitted data to determine the drug's benefit-risk ratio in the new context ⁽²⁹⁾.

1.2.7 Post-marketing surveillance

Once approved, the repurposed drug is monitored for real-world safety and effectiveness. Post-marketing surveillance involves:

Reporting and evaluation of adverse drug reactions (ADRs)
Collection of long-term safety data
Ongoing assessment of therapeutic outcomes

This stage ensures the continued safety and efficacy of the drug in the general population and may lead to further label updates or risk management plans ^(30,31).

Fig:01

1.3 Importance of Drug Reprofiling

Drug reprofiling plays an increasingly vital role in pharmaceutical innovation and global health strategy (32). Its importance stems from a combination of scientific, economic, and humanitarian benefits (33). Below are the key reasons why drug reprofiling has become a core component of modern drug development:

1.3.1 Time and cost efficiency

Traditional drug development is time-consuming and expensive (34). Drug reprofiling bypasses many early-stage steps—such as toxicology studies and Phase I clinical trials—because thesafety and pharmacokinetics of the drug are already known (35). This dramatically reduces development time and costs (36).

Fig:02

1.3.2 Lower risk of failure

Many drugs fail in clinical trials due to unforeseen toxicity or poor bioavailability. Reprofiled drugs, having already passed safety evaluations, present a lower risk during development and clinical testing for new indications ⁽³⁷⁾.

1.3.3 Fast response to public health emergencies

In emergency situations, such as infectious disease outbreaks, reprofiling enables a rapid therapeutic response ⁽³⁸⁾. This was evident during the COVID-19 pandemic, where several existing drugs were quickly tested and used under emergency authorizations ⁽³⁹⁾.

1.3.4 Maximizes existing drug libraries

Pharmaceutical companies often have a portfolio of previously developed compounds that were never commercialized⁽⁴⁰⁾. Reprofiling helps revive these assets by identifying new therapeutic areas, thus improving return on investment and resource utilization⁽⁴¹⁾.

1.2.5 Expands treatment for rare and neglected diseases

Reprofiling is particularly valuable for rare diseases and neglected tropical conditions where new drug development is not financially viable⁽⁴²⁾. It offers an accessible route to new therapies, improving global equity in healthcare⁽⁴³⁾.

1.2.6 Encourages interdisciplinary research and collaboration

The reprofiling process encourages collaboration between pharmacologists, clinicians, biochemists, and regulatory authorities ⁽⁴⁴⁾. This multidisciplinary effort promotes innovation and knowledge sharing across different sectors of healthcare and research ⁽⁴⁵⁾.

1.4 An Ideal Candidate for Drug Reprofiling

Choosing the best candidate is a crucial first stage in the drug reprofiling process that has a big impact on the overall outcome ⁽⁴⁶⁾. A therapeutic candidate with a thorough safety and pharmacokinetic profile is the best candidate for reprofiling since it enables researchers to avoid numerous expensive and time-consuming early phases of drug development ⁽⁴⁷⁾. Usually, a pool of previously approved medications, compounds that have been shelved, or medications that failed studies for reasons other than toxicity produces these candidates ⁽⁴⁸⁾.

Key Characteristics of an Ideal Candidate

1.4.1 Established safety and tolerability

Drugs that have already been tested in humans—either in completed clinical trials or approved for other indications—are prime candidates. Their safety profile is well-documented, reducing the risk of adverse outcomes and regulatory hurdles in the new indication ⁽⁴⁹⁾.

1.4.2 Known pharmacokinetic and pharmacodynamic properties

A deep understanding of the drug’s absorption, distribution, metabolism, excretion (ADME), and mechanism of action (MOA) makes it easier to predict its behavior in different disease conditions. This data also aids in determining dosage and treatment regimens for the new use⁽⁵⁰⁾.

1.4.3 Evidence of off-target or pleiotropic effects

Drugs that exhibit multiple mechanisms of action or off-target effects may offer therapeutic benefits beyond their original indication. These secondary effects, once considered side effects, can often serve as clues to potential new applications ⁽⁵¹⁾.

1.4.4 History of off-label use or clinical anecdotes

Drugs that have been used off-label or have anecdotal evidence suggesting benefits in other conditions are often strong reprofiling candidates. Such observations can serve as real-world indicators of therapeutic potential ⁽⁵²⁾.

1.4.5 Previously shelved drugs (non-safety reasons)

Many compounds are discontinued during development due to strategic decisions, commercial limitations, or failure to meet efficacy endpoints for a specific disease. If safety is not a concern, these shelved drugs may be re-evaluated for other indications ⁽⁵³⁾.

1.4.6 Chemical and formulation stability

Candidates with stable formulations, acceptable shelf-life, and scalable manufacturing processes are favourable, as these factors ease the transition into clinical testing for a new indication ⁽⁵⁴⁾.

Examples of reprofiled drugs:Several well-known drugs began their journey with one intended use but were successfully repurposed for entirely different therapeutic areas:

Thalidomide: Initially used as a sedative, later reprofiled for multiple myeloma and erythema nodosum leprosum ⁽⁵⁵⁾.
Sildenafil: Originally developed for angina, reprofiled for erectile dysfunction and pulmonary arterial hypertension ⁽⁵⁶⁾.
Minoxidil: First approved as an antihypertensive, later repositioned for androgenic alopecia ⁽⁵⁷⁾.

These success stories highlight how a deep understanding of drug biology, combined with clinical insight, can lead to effective reprofiling strategies.

1.5 Strategies for Drug Reprofiling

Drug reprofiling employs a diverse set of strategies to identify new therapeutic applications for existing drugs. These strategies range from observational and experimental approaches to systematic, molecular, and mechanism-based techniques. Choosing the right strategy depends on the type of drug, disease target, and available data ⁽⁵⁸⁾.

The following are major strategies widely used in drug reprofiling:

1. 1. Phenotypic modelling

Using this method, medications that produce phenotypic alterations akin to those seen in illness states are found.

Thalidomide, for instance, was first sold as a sedative but was later used to treat multiple myeloma after researchers noticed that it had anti-angiogenic effects in phenotypic screening⁽⁵⁹⁾.

1.5.2. Target based methods

Drugs that interact with particular molecular targets known to be involved in disease processes are identified using these techniques.

For instance, sildenafil (Viagra) was once created to treat hypertension and angina pectoris, but when researchers found that it specifically inhibited phosphodiesterase type 5 (PDE5), it was repurposed to treat erectile dysfunction ⁽⁶⁰⁾.

1.5.3. Knowledge-based methods

These make use of databases, literature, and current scientific knowledge to find possible new applications for already-approved medications. An illustration of this would be the repurposing of celecoxib, which was first used as an nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain and help relieve symptoms of arthritis. Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. showed that combining celecoxib with paclitaxel might be an effective treatment for ovarian cancer ⁽⁶¹⁾.

1.5.4. Signature-based methods

These techniques look for possible therapeutic matches by comparing drug induced gene expression profiles with illness signatures. For instance, researchers utilized the Connectivity Map to determine that the anticonvulsant topiramate's gene expression signature counteracted alterations in gene expression linked to alcohol addiction, leading to its repurposing for the treatment of alcohol dependency ⁽⁶²⁾.

1.5.6. Pathway-based and network-based reprofiling

Focuses on medications that alter biological networks or cellular signalling pathways that are prevalent in many disorders.

Beneficial when illnesses have common pathway-level mechanisms as opposed to distinct molecular targets.
Network-based techniques investigate drug interactions in gene-regulatory or protein-protein interaction (PPI) networks.

Rapamycin (sirolimus), originally an immunosuppressant that targets mTOR, was repurposed for treating tuberous sclerosis complex (TSC) after researchers discovered that TSC is characterized by hyperactivation of the mTOR pathway ⁽⁶³⁾.

1.5.7.Targeted mechanism-based reprofiling
This method compares the drug's pharmacological mechanism to the pathophysiology of an alternative illness.For instance, because neurodegenerative illnesses overlap inflammatory mechanisms, anti-inflammatory medications have been repurposed. An in-depth knowledge of pharmacology and pathophysiology is necessary for mechanism-based matching.

Example: Rapamycin (sirolimus), originally an immunosuppressant that targets mTOR, was repurposed for treating tuberous sclerosis complex ⁽⁶⁴⁾.

1.5.8. Molecular docking and structural modelling

This computational approach predicts how drugs bind to target proteins, enabling identification of new drug-target interactions i.e it helps predict binding affinity and interaction mode between a drug and a protein involved in another disease.

Example: Raloxifene, originally approved for osteoporosis, was repurposed for breast cancer prevention after molecular docking studies revealed its binding affinity to oestrogen receptors in breast tissue ⁽⁶⁵⁾.

2. Case Study And Applications

2.1 COVID-19

The COVID-19 pandemic triggered an urgent need for effective treatments ⁽⁶⁶⁾. Developing new drugs from scratch would take years, so researchers turned to drug repurposing—identifying existing drugs with potential to treat SARS-CoV-2⁽⁶⁷⁾. This strategy allowed for quicker deployment due to pre-existing safety data. Several drugs, originally designed for other diseases, were evaluated globally, with mixed outcomes⁽⁶⁸⁾.

Table 1: Comparative Table of Repurposed Drugs for COVID-19

Drug	Original Use	Mechanism of Action	COVID-19 Use	Efficacy Summary	Approval Status
Remdesivir^(69,70)	Ebola	Inhibits viral RNA polymerase	Moderate to severe cases	Shortens recovery time	FDA approved
Dexamethasone⁽⁷¹⁾	Inflammatory diseases	Corticosteroid; reduces inflammation	Severe cases with oxygen support	Reduces mortality	Globally recommended
Favipiravir⁽⁷²⁾	Influenza	Inhibits RNA polymerase	Mild to moderate cases	Mixed results	Emergency use in some countries
Hydroxychloroquine⁽⁷³⁾	Malaria, Lupus	Alters endosomal pH	Early-stage use	No proven benefit	Not recommended
Ivermectin⁽⁷⁴⁾	Parasitic infections	Inhibits importin protein pathway	Mild cases (off-label)	Conflicting evidence	Not recommended
Tocilizumab⁽⁷⁵⁾	Rheumatoid arthritis	IL-6 receptor antagonist	Severe cases with inflammation	Improves survival with steroids	Conditional approval
Baricitinib⁽⁷⁶⁾	Rheumatoid arthritis	JAK inhibitor	Moderate to severe cases	Improves outcomes with Remdesivir	Emergency use authorized

2.2. Neurodegenerative Disorders

Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD) are characterized by progressive neuronal dysfunction and lack effective curative treatments(77,78). Traditional drug development for these diseases faces high failure rates and long timelines. Repurposing existing drugs with known safety profiles can significantly reduce the cost and time of developing new therapies, especially for rare or complex CNS disorders(79,80,81).

Flowchart: Repurposing Pipeline for Neurodegenerative Diseases

FDA-Approved Drug → Mechanistic Screening → Disease Model Testing → Phase I/II Trials in ND Patients → Regulatory Repositioning(87)

Table 2: Comparative Table of Repurposed Drugs For ND

Drug	Original Use	ND Target	Mechanism
Memantine⁽⁸²⁾	Alzheimer’s	PD, ALS	NMDA receptor antagonist
Riluzole⁽⁸³⁾	ALS	AD, HD	Glutamate inhibition
Rasagiline⁽⁸⁴⁾	Parkinson’s	AD	MAO-B inhibition
Metformin⁽⁸⁵⁾	Type 2 Diabetes	AD, PD	AMPK activation
Nilotinib⁽⁸⁶⁾	Leukemia	PD, AD	Tyrosine kinase inhibition

2.3cancer

Cancer remains a major global health challenge. The high cost and time-consuming nature of novel drug development make drug repurposing an attractive alternative. The traditional path of cancer drug development is lengthy, high-risk, and expensive⁽⁸⁸⁾.

2.3.1. Colon and Breast Cancer

Table 3 : Comparative Table of Repurposed Drugs in Colon and Breast

Drug	Original Use	Cancer Target	Mechanism
Metformin⁽⁸⁹⁾	Type 2 Diabetes	Breast, Colon	AMPK activation, mTOR inhibition
Aspirin⁽⁹⁰⁾	Analgesic/NSAID	Colon	COX inhibition, anti-inflammatory
Disulfiram⁽⁹¹⁾	Alcohol dependence	Breast, Colon	ROS generation, proteasome inhibition
Itraconazole⁽⁹²⁾	Antifungal	Breast, Colon	Hedgehog pathway, angiogenesis inhibition
Propranolol⁽⁹³⁾	Hypertension	Breast	Beta-adrenergic blockade, anti-angiogenesis

Drug Repurposing Strategy Flowchart

Drug with Known Safety → Preclinical Testing in Cancer Models → Mechanistic Studies → Clinical Trials (Phase I/II) → Potential New Indication⁽⁹⁴⁾

2.4. Parasitic Infection

Parasitic infections such as malaria, leishmaniasis, trypanosomiasis, and schistosomiasis affect millions globally, particularly in tropical and subtropical regions ⁽⁹⁵⁾. The traditional drug discovery pipeline is time-consuming and expensive, prompting interest in drug repurposing — using existing approved or investigational drugs for new therapeutic indications^(96,97).

Table 4: Comparative Table of Repurposed Drugs For Parasitic Infection

Drug	Original Use	Repurposed For	Mechanism in Parasitic Infection	Status
Miltefosine⁽⁹⁸⁾	Breast cancer	Leishmaniasis	Disrupts parasite cell membrane	Approved
Nitazoxanide⁽⁹⁹⁾	Diarrhea (Cryptosporidium)	Giardiasis, Amebiasis	Inhibits PFOR enzyme-dependent electron transfer	Approved
Metronidazole⁽¹⁰⁰⁾	Anaerobic bacterial infections	Amoebiasis, Giardiasis	DNA synthesis inhibition in anaerobic organisms	Approved
Eflornithine⁽¹⁰¹⁾	Cancer (ornithine decarboxylase inhibitor)	Trypanosomiasis	Inhibits polyamine biosynthesis	Approved (WHO)
Chloroquine⁽¹⁰²⁾	Malaria	Amebiasis, Leishmaniasis	Interferes with heme detoxification in parasites	Repurposing trials

1. . Auto Immune Diseases

Autoimmune diseases result from immune system dysregulation⁽¹⁰³⁾. Drug repurposing in this domain focuses on utilizing existing immunomodulatory or anti-inflammatory drugs developed for other indications⁽¹⁰⁴⁾.

Table 5: Comparative Table Of Repurposed Drugs For Autoimmune Diseases

Drug	Original use	Repurposed Autoimmune Use	Mechanism
Hydroxychloroquine⁽¹⁰⁵⁾	Antimalarial	SLE, Rheumatoid Arthritis	TLR inhibition, reduces antigen presentation
Methotrexate⁽¹⁰⁶⁾	Chemotherapy (cancer)	Psoriasis, Crohn’s Disease	Inhibits folate metabolism; immunosuppressive
Azathioprine⁽¹⁰⁷⁾	Anticancer(leukemia)	Systemic sclerosis, Myositis	Purine synthesis inhibition, reduces T/B cells
Infliximab, Adalimumab⁽¹⁰⁸⁾	Anti-TNF (Crohn’s)	RA, Psoriasis, Ankylosing Spondylitis	Neutralizes TNF-α
Tofacitinib, Baricitinib⁽¹⁰⁹⁾	JAK inhibitors	RA, Psoriasis	Inhibits JAK/STAT pathway

2.6. Rare Diseases

Rare diseases, also known as orphan diseases, are conditions that affect a small percentage of the population⁽¹¹⁰⁾. These diseases are often genetic in origin, chronic, and life-threatening, with limited treatment options available ⁽¹¹¹⁾. Due to their low prevalence, rare diseases often face challenges in diagnosis, research, and drug development, making awareness and innovation in this field critically important⁽¹¹²⁾.

Table 6: Comparative Table Of Repurposed Drugs For Rare Diseases

Drug	Original Use	Repurposed Rare Disease Use	Mechanism
Penicillamine⁽¹¹³⁾	Anti-leukemic	Wilson’s disease	Copper chelator
Valproic Acid⁽¹¹⁴⁾	Antiepileptic	Niemann–Pick Type C	HDAC inhibition, improves lysosomal function
Lisinopril⁽¹¹⁵⁾	Hypertension (ACE inhibitor)	Alport syndrome (renal disease)	Reduces glomerular pressure
Tacrolimus⁽¹¹⁶⁾	Immunosuppressant (transplants)	Myasthenia Gravis ,DMD	T-cell suppression
Azithromycin⁽¹¹⁷⁾	Antibiotic (macrolide)	Cystic fibrosis	Anti-inflammatory in airway
Desipramine⁽¹¹⁸⁾	Antidepressant	Rett syndrome	Enhances norepinephrine, possible neuroprotective effect

2.7. Infectious Diseases

Infectious diseases are disorders caused by microorganisms such as bacteria, viruses, fungi, or parasites. These diseases can spread directly or indirectly from one person to another, through contaminated food, water, air, or vectors like mosquitoes⁽¹

Table 7: Comparative Table Of Repurposed Drugs For Infectious Diseases

Drug	Original Use	Repurposed Infectious Use	Mechanism
Chloroquine, Hydroxychloroquine⁽¹²⁰⁾	Antimalarial	COVID-19 (initially), Viral infections	Endosomal pH modulation, antiviral entry blocker
Lopinavir-Ritonavir⁽¹²¹⁾	Antiviral (HIV protease inhibitor)	COVID-19, SARS	Viral protease inhibition
Ivermectin⁽¹²²⁾	Antiparasitic (helminths)	COVID-19 (investigational)	Blocks viral nuclear transport proteins
Fluvoxamine⁽¹²³⁾	Antidepressant (SSRI)	COVID-19	S1R agonist, reduces cytokine storm
Azithromycin⁽¹²⁴⁾	Antibiotic (macrolide)	COVID-19 (with hydroxychloroquine)	Anti-inflammatory and possible antiviral
Indomethacin⁽¹²⁵⁾	NSAID	Dengue, Zika (supportive)	Antiviral effect in vitro via prostaglandin inhibition

2.8. Cardiovascular Diseases

Cardiovascular diseases remain the leading cause of mortality globally⁽¹²⁶⁾. Drug reprofiling in cardiology aims to find new therapeutic benefits of existing drugs, particularly for heart failure, hypertension, arrhythmias, atherosclerosis, and pulmonary hypertension.It saves time and cost compared to de novo drug development^(127,128).

Table 8 : Comparative Table Of Repurposed Drugs For CVD

Drug	Original indication	Repurposed for	Mechanism in CVD Context
Empagliflozin, Dapagliflozin⁽¹²⁹⁾	Type 2 Diabetes	Heart Failure (HFrEF, HFpEF)	SGLT2 inhibitors; improve cardiac metabolism and reduce preload
Sildenafil, Tadalafil⁽¹³⁰⁾	Erectile Dysfunction	Pulmonary Arterial Hypertension (PAH)	PDE5 inhibition → vasodilation of pulmonary vasculature
Methotrexate (low dose)⁽¹³¹⁾	Cancer (chemotherapy)	Atherosclerosis, Post-MI remodeling	Anti-inflammatory (IL-1β, CRP reduction)
Colchicine⁽¹³²⁾	Immunosuppressant (RA)	Pericarditis, Post -MI inflammation	Inhibits neutrophil migration and inflammasome activation
Statins (e.g. Atorvastatin)⁽¹³³⁾	Lipid Disorders	Heart Failure, Stroke	Beyond lipid lowering: plaque stabilization, anti-inflammatory
Fluoxetine, Sertraline⁽¹³⁴⁾	Antidepressants(SSRIs)	Ischemic heart disease, stroke prevention	Platelet inhibition and mood stabilization in cardiac patients
Liraglutide, Semaglutide⁽¹³⁵⁾	Antidiabetic (GLP-1 RA)	CVD risk reduction in diabetes	Improves endothelial function and weight reduction
Ranolazine⁽¹³⁶⁾	Antianginal	Heart failure with preserved ejection fraction (HFpEE)	Late sodium current inhibition → improves myocardial relaxation

Clinical Benefits of Cardiovascular Drug Repurposing:

Cost-effectiveness: Avoids early-phase trials.
Reduced time to market.
Multifactorial benefit: Many CVDs have metabolic, inflammatory, and vascular components that benefit from multitarget drugs.

Enhanced compliance: Patients with comorbidities (e.g., diabetes + CVD) benefit from dual-action drugs like SGLT2 inhibitors⁽¹³⁷⁾.

Fig:03

2.9.Metabolic Disorders

Metabolic disorders are conditions that disrupt normal metabolism — the process your body uses to convert food into energy and building blocks for cells. These disorders can be inherited (genetic) or acquired due to lifestyle, disease, or medication⁽¹³⁸⁾.

Table 9: Comparative Table Of Repurposed Drugs For MD

Drug	Original Use	Repurposed Use	Mechanism
Metformin⁽¹³⁹⁾	Type 2 Diabetes	PCOS, cancer, anti-aging	Activates AMPK, reduces hepatic glucose production
Thiazolidinediones (e.g., Pioglitazone)⁽¹⁴⁰⁾	Type 2 Diabetes	NAFLD, PCOS	PPARγ agonism, improves insulin sensitivity
SGLT2 Inhibitors (e.g., Dapagliflozin)⁽¹⁴¹⁾	Diabetes	Heart failure, CKD	Promotes glucosuria, reduces cardiac stress
Statins⁽¹⁴²⁾	Hyperlipidemia	Alzheimer's, NAFLD	Inhibits HMG-CoA reductase, anti-inflammatory
Colesevelam⁽¹⁴³⁾	Hyperlipidemia	Type 2 Diabetes	Bile acid sequestration improves glycemic control
Topiramate⁽¹⁴⁴⁾	Epilepsy	Obesity, binge eating disorder	Inhibits carbonic anhydrase, suppresses appetite
Hydroxychloroquine⁽¹⁴⁵⁾	Malaria	Type 2 Diabetes, RA	Reduces inflammation, improves insulin sensitivity
Bromocriptine⁽¹⁴⁶⁾	Parkinson’s Disease	Type 2 Diabetes	Dopamine D2 receptor agonist; resets circadian rhythm
Orlistat⁽¹⁴⁷⁾	Obesity	Type 2 Diabetes	Inhibits lipase, reduces fat absorption

Fig:04

2.10.Drug Repurposing For Kidney Ailments

Drug reprofiling (or repurposing) for kidney ailments is a powerful strategy for finding new therapeutic uses for existing drugs in the treatment of kidney diseases. This approach is particularly valuable given the high unmet medical needs in chronic kidney disease (CKD), acute kidney injury (AKI), and other renal disorders. By leveraging drugs with established safety profiles, researchers can accelerate the treatment options for kidney patients^{(148,149,150)}.

Table 10: Comparative Table Of Repurposed Drugs For Kidney Ailments

Drug	Original Use	Repurposed Use in Kidney Disease	Mechanism of Action	Kidney Benefit
SGLT2 Inhibitors (e.g., Dapagliflozin, Empagliflozin)⁽¹⁵¹⁾	Type 2 Diabetes	CKD, Heart Failure	Inhibit SGLT2 → glucosuria, ↓ glomerular pressure	Slows CKD progression, cardio-renal protection
Epoetin, Darbepoetin⁽¹⁵²⁾	Anemia in cancer	Anemia in CKD	Stimulates erythropoiesis (RBC production)	Treats CKD-associated anemia
ACE Inhibitors (e.g., Ramipril)⁽¹⁵³⁾	Hypertension, Heart Failure	CKD, Proteinuria	Inhibits RAAS → ↓ BP and glomerular pressure	Reduces proteinuria, protects renal function
Statins (e.g., Atorvastatin)⁽¹⁵⁴⁾	Hyperlipidemia	CKD, Proteinuria	Inhibits HMG-CoA reductase → ↓ cholesterol, anti-inflammatory	↓ Cardiovascular risk, antiproteinuric effect
Spironolactone, Eplerenone⁽¹⁵⁵⁾	Hypertension, Heart Failure	CKD, Proteinuria	Aldosterone antagonism → ↓ sodium retention, fibrosis	Reduces proteinuria, glomerular fibrosis
Colchicine⁽¹⁵⁶⁾	Gout, FMF	CKD (fibrosis)	Inhibits inflammasome → anti-fibrotic	↓ Kidney fibrosis and inflammation
N-acetylcysteine (NAC)⁽¹⁵⁷⁾	Acetaminophen overdose	AKI, Contrast-Induced Nephropathy	Antioxidant, scavenges ROS	Prevents/treats AKI, especially post-contrast
Sirolimus (Rapamycin)⁽¹⁵⁸⁾	Organ transplant immunosuppressant	Alport Syndrome, FSGS	mTOR inhibition → anti-proliferative, anti-fibrotic	↓ Proteinuria, slows glomerular scarring
Pentoxifylline⁽¹⁵⁹⁾	Peripheral vascular disease	Diabetic Nephropathy	Improves blood flow, anti-inflammatory	↓ Proteinuria, improves kidney function
Lithium⁽¹⁶⁰⁾	Bipolar disorder	Renal regeneration (experimental)	Inhibits GSK-3 → cell regeneration	Promotes renal repair (preclinical stage)

2.11.HMG CoA – Reductase Inhibitor

Table 11: Comparative Table Of Repurposed HMG CoA – Reductase Inhibitors

Drug Name	Original Indication	Repurposed Use	Mechanism Behind Reprofiling	Status
Atorvastatin⁽¹⁶¹⁾	Hyperlipidemia	Alzheimer's disease, Multiple sclerosis	Anti-inflammatory, improves cerebral blood flow	Clinical trials, observational
Simvastatin⁽¹⁶²⁾	Hyperlipidemia	Rheumatoid arthritis, Osteoporosis	Reduces inflammation, affects bone metabolism	Investigational
Lovastatin⁽¹⁶³⁾	Hyperlipidemia	Cancer (breast, prostate, glioma)	Inhibits tumor cell proliferation via mevalonate pathway suppression	Preclinical to early trials
Rosuvastatin⁽¹⁶⁴⁾	Hyperlipidemia	Pulmonary hypertension	Improves endothelial function, reduces vascular remodeling	Investigational

CONCLUSION

Drug reprofiling has emerged as a key tactic in modern medicine, transforming the way existing drugs are used for new purposes. By avoiding early-stage safety evaluations, it significantly reduces time, cost, and risk when compared to traditional drug development. Its use spans a wide range of illnesses, from cancer and neurodegenerative conditions to rare and infectious diseases, indicating its adaptability and impact on global health. The integration of computational, observational, and experimental approaches has expanded its scope, improving treatment accessibility for underserved populations and enabling faster responses to public health emergencies. Drug reprofiling is expected to remain a crucial element of pharmaceutical innovation as interdisciplinary collaboration increases and regulatory pathways shift, maximising available resources and driving worldwide advances in precision and personalised medicine.

ACKNOWLEGEMENT

We, students of 7th semester B. Pharm, take the privilege to acknowledge to all those who helped me in the project work entitled as “Drug Reprofiling in the Age of Necessity: A Strategic-Clinical Synthesis for Therapeutic Clinical Outcome”. At first, we express our deep sense of gratitude indebtedness to the Department of Pharmacology of Mar Dioscorus College of Pharmacy, for helping us in the completion of our practice school. We are extremely thankful to DR. PREEJA. G. PILLAI, our principal, for her guidance and support throughout the work. We owe our profound recognition to DR. SINCHU YESUDANAM, our guide for enlightening us with knowledge, valuable suggestions and for her remarkable encouragement which made us complete our work. We are also grateful to DR. JOYAMMA VARKEY for providing us with valuable education throughout our practice school. We express our sincere thanks to one and all that accompanied and helped throughout our educational career.

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Dr. Sinchu Yesudanam

Corresponding author

Mar Dioscorus College of Pharmacy.

Anshu Shyjin

Co-author

Mar Dioscorus College of Pharmacy.

M. Muhammed Aslam

Co-author

Mar Dioscorus College of Pharmacy.

Dr. Sinchu Yesudanam*, Anshu Shyjin, M. Muhammed Aslam, Drug Reprofiling in the Age of Necessity: A Strategic-Clinical Synthesis for Therapeutic Clinical Outcome, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 8, 1667-1688. https://doi.org/10.5281/zenodo.16881340

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Drug Reprofiling in the Age of Necessity: A Strategic-Clinical Synthesis for Therapeutic Clinical Outcome

Abstract

Keywords

Introduction

Reference

Dr. Sinchu Yesudanam

Anshu Shyjin

M. Muhammed Aslam

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