scholarly journals Repurposing – second life for drugs

Pharmacia ◽  
2022 ◽  
Vol 69 (1) ◽  
pp. 51-59
Author(s):  
Porkodi Ayyar ◽  
Umamaheswari Subramanian
Keyword(s):  
Drug Discovery ◽  
Second Life ◽  
Drug Repurposing ◽  
New Drugs ◽  
Protein Targets ◽  
Medical Needs ◽  
New Drug ◽  
Patent Expiry ◽  
Traditional Drug ◽  
Increasing Demand

Drug repurposing refers to finding new indications for existing drugs. The paradigm shift from traditional drug discovery to drug repurposing is driven by the fact that new drug pipelines are getting dried up because of mounting Research & Development (R&D) costs, long timeline for new drug development, low success rate for new molecular entities, regulatory hurdles coupled with revenue loss from patent expiry and competition from generics. Anaemic drug pipelines along with increasing demand for newer effective, cheaper, safer drugs and unmet medical needs call for new strategies of drug discovery and, drug repurposing seems to be a promising avenue for such endeavours. Drug repurposing strategies have progressed over years from simple serendipitous observations to more complex computational methods in parallel with our ever-growing knowledge on drugs, diseases, protein targets and signalling pathways but still the knowledge is far from complete. Repurposed drugs too have to face many obstacles, although lesser than new drugs, before being successful.

scholarly journals Drug Repurposing: A Paradigm Shift in Drug Discovery

2020 ◽  
Vol 5 (04) ◽  
pp. 60-68
Author(s):  
Saravanan Jayaram ◽  
Emdormi Rymbai ◽  
Deepa Sugumar ◽  
Divakar Selvaraj
Keyword(s):  
Drug Discovery ◽  
Success Rate ◽  
Chemical Structure ◽  
Target Identification ◽  
Drug Repurposing ◽  
New Drugs ◽  
Attractive Option ◽  
Traditional Drug ◽  
Repurposed Drugs

The traditional methods of drug discovery and drug development are a tedious, complex, and costly process. Target identification, target validation; lead identification; and lead optimization are a lengthy and unreliable process that further complicates the discovery of new drugs. A study of more than 15 years reports that the success rate in the discovery of new drugs in the fields of ophthalmology, cardiovascular, infectious disease, and oncology to be 32.6%, 25.5%, 25.2% and 3.4%, respectively. A tedious and costly process coupled with a very low success rate makes the traditional drug discovery a less attractive option. Therefore, an alternative to traditional drug discovery is drug repurposing, a process in which already existing drugs are repurposed for conditions other than which were originally intended. Typical examples of repurposed drugs are thalidomide, sildenafil, memantine, mirtazapine, mifepristone, etc. In recent times, several databases have been developed to hasten drug repurposing based on the side effect profile, the similarity of chemical structure, and target site. This work reviews the pivotal role of drug repurposing in drug discovery and the databases currently available for drug repurposing.

scholarly journals Drug Repurposing (DR): An Emerging Approach in Drug Discovery

2020 ◽  
Author(s):  
Mithun Rudrapal ◽  
Shubham J. Khairnar ◽  
Anil G. Jadhav
Keyword(s):  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Development Program ◽  
Drug Repurposing ◽  
New Drugs ◽  
Time Saving ◽  
Biological Targets ◽  
Drug Molecules ◽  
Traditional Drug

Drug repurposing (DR) (also known as drug repositioning) is a process of identifying new therapeutic use(s) for old/existing/available drugs. It is an effective strategy in discovering or developing drug molecules with new pharmacological/therapeutic indications. In recent years, many pharmaceutical companies are developing new drugs with the discovery of novel biological targets by applying the drug repositioning strategy in drug discovery and development program. This strategy is highly efficient, time saving, low-cost and minimum risk of failure. It maximizes the therapeutic value of a drug and consequently increases the success rate. Thus, drug repositioning is an effective alternative approach to traditional drug discovery process. Finding new molecular entities (NME) by traditional or de novo approach of drug discovery is a lengthy, time consuming and expensive venture. Drug repositioning utilizes the combined efforts of activity-based or experimental and in silico-based or computational approaches to develop/identify the new uses of drug molecules on a rational basis. It is, therefore, believed to be an emerging strategy where existing medicines, having already been tested safe in humans, are redirected based on a valid target molecule to combat particularly, rare, difficult-to-treat diseases and neglected diseases.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

Computational approaches for drug discovery against trypanosomatid-caused diseases

Parasitology ◽  
2020 ◽  
Vol 147 (6) ◽  
pp. 611-633 ◽  
Author(s):  
Claudio A. Pereira ◽  
Melisa Sayé ◽  
Chantal Reigada ◽  
Ariel M. Silber ◽  
Guillermo R. Labadie ◽  
...  
Keyword(s):  
Selection Criteria ◽  
Disease Burden ◽  
Neglected Tropical Diseases ◽  
Drug Repurposing ◽  
New Drugs ◽  
Computational Simulations ◽  
Protein Targets ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds ◽  
Research Investments

AbstractDuring three decades, only about 20 new drugs have been developed for malaria, tuberculosis and all neglected tropical diseases (NTDs). This critical situation was reached because NTDs represent only 10% of health research investments; however, they comprise about 90% of the global disease burden. Computational simulations applied in virtual screening (VS) strategies are very efficient tools to identify pharmacologically active compounds or new indications for drugs already administered for other diseases. One of the advantages of this approach is the low time-consuming and low-budget first stage, which filters for testing experimentally a group of candidate compounds with high chances of binding to the target and present trypanocidal activity. In this work, we review the most common VS strategies that have been used for the identification of new drugs with special emphasis on those applied to trypanosomiasis and leishmaniasis. Computational simulations based on the selected protein targets or their ligands are explained, including the method selection criteria, examples of successful VS campaigns applied to NTDs, a list of validated molecular targets for drug development and repositioned drugs for trypanosomatid-caused diseases. Thereby, here we present the state-of-the-art of VS and drug repurposing to conclude pointing out the future perspectives in the field.

scholarly journals TDR Targets 6: driving drug discovery for human pathogens through intensive chemogenomic data integration

2019 ◽  
Author(s):  
Lionel Urán Landaburu ◽  
Ariel J Berenstein ◽  
Santiago Videla ◽  
Parag Maru ◽  
Dhanasekaran Shanmugam ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Data Integration ◽  
Bioactive Compounds ◽  
Drug Repurposing ◽  
Network Models ◽  
Model Organisms ◽  
Human Pathogens ◽  
Protein Targets ◽  
Chemical Inhibitors ◽  
Automated Screening

Abstract The volume of biological, chemical and functional data deposited in the public domain is growing rapidly, thanks to next generation sequencing and highly-automated screening technologies. These datasets represent invaluable resources for drug discovery, particularly for less studied neglected disease pathogens. To leverage these datasets, smart and intensive data integration is required to guide computational inferences across diverse organisms. The TDR Targets chemogenomics resource integrates genomic data from human pathogens and model organisms along with information on bioactive compounds and their annotated activities. This report highlights the latest updates on the available data and functionality in TDR Targets 6. Based on chemogenomic network models providing links between inhibitors and targets, the database now incorporates network-driven target prioritizations, and novel visualizations of network subgraphs displaying chemical- and target-similarity neighborhoods along with associated target-compound bioactivity links. Available data can be browsed and queried through a new user interface, that allow users to perform prioritizations of protein targets and chemical inhibitors. As such, TDR Targets now facilitates the investigation of drug repurposing against pathogen targets, which can potentially help in identifying candidate targets for bioactive compounds with previously unknown targets. TDR Targets is available at https://tdrtargets.org.

scholarly journals Recent Advances in In Silico Target Fishing

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5124 ◽  
Author(s):  
Salvatore Galati ◽  
Miriana Di Stefano ◽  
Elisa Martinelli ◽  
Giulio Poli ◽  
Tiziano Tuccinardi
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Drug Targets ◽  
Biological Activities ◽  
Protein Structures ◽  
Drug Repurposing ◽  
Specific Protein ◽  
Protein Targets ◽  
Drug Candidates ◽  
Target Fishing

In silico target fishing, whose aim is to identify possible protein targets for a query molecule, is an emerging approach used in drug discovery due its wide variety of applications. This strategy allows the clarification of mechanism of action and biological activities of compounds whose target is still unknown. Moreover, target fishing can be employed for the identification of off targets of drug candidates, thus recognizing and preventing their possible adverse effects. For these reasons, target fishing has increasingly become a key approach for polypharmacology, drug repurposing, and the identification of new drug targets. While experimental target fishing can be lengthy and difficult to implement, due to the plethora of interactions that may occur for a single small-molecule with different protein targets, an in silico approach can be quicker, less expensive, more efficient for specific protein structures, and thus easier to employ. Moreover, the possibility to use it in combination with docking and virtual screening studies, as well as the increasing number of web-based tools that have been recently developed, make target fishing a more appealing method for drug discovery. It is especially worth underlining the increasing implementation of machine learning in this field, both as a main target fishing approach and as a further development of already applied strategies. This review reports on the main in silico target fishing strategies, belonging to both ligand-based and receptor-based approaches, developed and applied in the last years, with a particular attention to the different web tools freely accessible by the scientific community for performing target fishing studies.

Proposed Standards and Regulatory Mechanisms for New Homeopathic Drug Development

2021 ◽  
Vol 34 (04) ◽  
pp. 283-290
Author(s):  
Gitanjali Talele ◽  
Rajesh Shah
Keyword(s):  
Drug Discovery ◽  
Drug Development ◽  
Regulatory Mechanism ◽  
New Drugs ◽  
Regulatory Mechanisms ◽  
Regulatory Body ◽  
Market Authorisation ◽  
New Drug ◽  
Homeopathic Drug ◽  
Basic Proposition

Abstract Introduction Researchers working with new insights and new targets in new drug discovery in the homeopathy space observe that the path of drug-development and market authorisation has been less travelled and the pathway is not yet well-mapped. The need of the time is to define clear guidelines and regulatory mechanisms to facilitate the process of new drug discovery. Overview The article is about the proposed methods for identifying the new homeopathic substances for therapeutic use. An overview of the current regulations for drug development in India is discussed in this article. Method of new drug development in homeopathy, standards and regulatory mechanism for approval of new drugs are proposed with few illustrations and references. An introductory plan, based on the perspective and experience of researcher, practitioner, academician and inventor for drug discovery is proposed. Discussion An urgent need for setting up the guidelines for new drug discovery has been identified and a basic proposition is made for the same, suggesting practical, pragmatic and achievable measures, and independent regulatory body to encourage drug development and research.

Harnessing Drug Repurposing for Exploration of New Diseases: An Insight to Strategies and Case Studies

2020 ◽  
Vol 20 ◽  
Author(s):  
Priti Jain ◽  
Shreyans K Jain ◽  
Munendra Jain
Keyword(s):  
Drug Discovery ◽  
Case Studies ◽  
Drug Repositioning ◽  
Pediatric Population ◽  
Clinical Status ◽  
Drug Repurposing ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Traditional Drug ◽  
Approved Drugs

Background: Traditional drug discovery is time consuming, costly, and risky process. Owing to the large investment, excessive attrition, and declined output; drug repurposing has become a blooming approach for the identification and development of new therapeutics. The method has gained momentum in the past few years and has resulted in many excellent discoveries. Industries are resurrecting the failed and shelved drugs to save time and cost. The process accounts for approximately 30% of the new US Food and Drug Administration approved drugs and vaccines in recent years. Methods: A systematic literature search using appropriate keywords were made to identify articles discussing the different strategies being adopted for repurposing and various drugs that have been/are being repurposed. Results: This review aims to describe the comprehensive data about the various strategies (Blinded search, computational approaches, and experimental approaches) used for the repurposing along with success case studies (treatment for orphan diseases, neglected tropical disease, neurodegenerative diseases, and drugs for pediatric population). It also inculcates an elaborated list of more than 100 drugs that have been repositioned, approaches adopted, and their present clinical status. We have also attempted to incorporate the different databases used for computational repurposing. Conclusion: The data presented is proof that drug repurposing is a prolific approach circumventing the issues poised by conventional drug discovery approaches. It is a highly promising approach and when combined with sophisticated computational tools it also carries high precision. The review would help researches in prioritizing the drug-repositioning method much needed to flourish the drug discovery research.

scholarly journals Drug Repurposing in Neurological Diseases: Opportunities and Challenges

2020 ◽  
Author(s):  
Xiao-Yuan Mao
Keyword(s):  
Neurological Diseases ◽  
Drug Repurposing ◽  
New Drugs ◽  
Drug Candidates ◽  
Therapeutic Benefits ◽  
Therapeutic Value ◽  
Traditional Drug ◽  
Approved Drugs ◽  
Structure Complexity ◽  
Refractory Diseases

Drug repurposing or repositioning refers to “studying of clinically approved drugs in one disease to see if they have therapeutic value and do not trigger side effects in other diseases.” Nowadays, it is a vital drug discovery approach to explore new therapeutic benefits of existing drugs or drug candidates in various human diseases including neurological disorders. This approach overcomes the shortage faced during traditional drug development in grounds of financial support and timeline. It is especially hopeful in some refractory diseases including neurological diseases. The feature that structure complexity of the nervous system and influence of blood–brain barrier permeability often becomes more difficult to develop new drugs in neuropathological conditions than diseases in other organs; therefore, drug repurposing is particularly of utmost importance. In this chapter, we discuss the role of drug repurposing in neurological diseases and make a summarization of repurposing candidates currently in clinical trials for neurological diseases and potential mechanisms as well as preliminary results. Subsequently we also outline drug repurposing approaches and limitations and challenges in the future investigations.

scholarly journals Mapping the SARS-CoV-2–Host Protein–Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics

2021 ◽  
Vol 22 (2) ◽  
pp. 532
Author(s):  
Rosa Terracciano ◽  
Mariaimmacolata Preianò ◽  
Annalisa Fregola ◽  
Corrado Pelaia ◽  
Tiziana Montalcini ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Drug Discovery ◽  
Protein Interactions ◽  
Drug Targets ◽  
Affinity Purification ◽  
Drug Repurposing ◽  
Host Protein ◽  
Host Cells ◽  
Traditional Drug ◽  
Approved Drugs

Protein–protein interactions (PPIs) are the vital engine of cellular machinery. After virus entry in host cells the global organization of the viral life cycle is strongly regulated by the formation of virus-host protein interactions. With the advent of high-throughput -omics platforms, the mirage to obtain a “high resolution” view of virus–host interactions has come true. In fact, the rapidly expanding approaches of mass spectrometry (MS)-based proteomics in the study of PPIs provide efficient tools to identify a significant number of potential drug targets. Generation of PPIs maps by affinity purification-MS and by the more recent proximity labeling-MS may help to uncover cellular processes hijacked and/or altered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing promising therapeutic targets. The possibility to further validate putative key targets from high-confidence interactions between viral bait and host protein through follow-up MS-based multi-omics experiments offers an unprecedented opportunity in the drug discovery pipeline. In particular, drug repurposing, making use of already existing approved drugs directly targeting these identified and validated host interactors, might shorten the time and reduce the costs in comparison to the traditional drug discovery process. This route might be promising for finding effective antiviral therapeutic options providing a turning point in the fight against the coronavirus disease-2019 (COVID-19) outbreak.

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