Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate

: Since a decade, it has been observed that there is remarkable decrease in the quantum of novel clinically approved drugsin spite of modernization in research and development process. We have highlighted repositioning of drugs as a methodology that has found new therapeutic implications for clinically approved drugs but with different indications. This can be considered as an upbringing strategy to deliver timely and cost-effective solutions which still needexplorationtoget over the shortage of number of novel drugs reaching market. This review focuses on activity-based drug repositioning approach, which is used to explore new uses of known drugs that are already approved for specific indications and are now being used for other indications on the basis ofthe fact that single drug interacts with multiple targets. It also includes current research trends related to drug repositioning which depends on strong knowledge of medicinal chemistry and involves elucidation of mechanisms of action and validation of novel targets. The review highlights theimportance totheusage of computational tools and databases of various forms for drug repositioning purposes which have enhanced the ability to pose reasonable and testable hypotheses. The critical nature of this aspect is obvious in cases where data gathered from in vitro or animal models do not confirm in subsequent clinical trials. Hence, considering positive outcomes of drug repositioning, it can be surmised that this approach can serve as promising one that can develop into a robust drug discovery strategy.

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Chemogenomic Approaches for Revealing Drug target Interactions in Drug Discovery

Current Genomics ◽

10.2174/1389202922666210920125800 ◽

2021 ◽

Vol 22 ◽

Author(s):

Harshita Bhargava ◽

Amita Sharma ◽

Prashanth Suravajhala

Keyword(s):

Drug Discovery ◽

In Silico ◽

Drug Target ◽

Drug Repositioning ◽

Personalised Medicine ◽

Classification Problem ◽

Target Interaction ◽

Advantages And Disadvantages

: The drug discovery process has been a crucial and cost-intensive process. This cost is not only monetary but also involves risks, time, and labour that are incurred while introducing a drug in the market. In order to reduce this cost and the risks associated with the drugs that may result in severe side effects, the in silico methods have gained popularity in recent years. These methods have had a significant impact on not only drug discovery but also the related areas such as drug repositioning, drug-target interaction prediction, drug side effect prediction, personalised medicine, etc. Amongst these research areas predicting interactions between drugs and targets forms the basis for drug discovery. The availability of big data in the form of bioinformatics, genetic databases, along with computational methods, have further supported data-driven decision-making. The results obtained through these methods may be further validated using in vitro or in vivo experiments. This validation step can further justify the predictions resulting from in silico approaches, further increasing the accuracy of the overall result in subsequent stages. A variety of approaches are used in predicting drug-target interactions, including ligand-based, molecular docking based and chemogenomic-based approaches. This paper discusses the chemogenomic methods, considering drug target interaction as a classification problem on whether or not an interaction between a particular drug and target would serve as a basis for understanding drug discovery/drug repositioning. We present the advantages and disadvantages associated with their application.

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Evaluation of Drug Repositioning by Molecular Docking of Pharmaceutical Resources to Identification of Potential SARS-CoV-2 Viral Inhibitors

10.5772/intechopen.101395 ◽

2022 ◽

Author(s):

Fatemeh Hosseini ◽

Mehrdad Azin ◽

Hamideh Ofoghi ◽

Tahereh Alinejad

Keyword(s):

Molecular Docking ◽

Drug Discovery ◽

In Silico ◽

De Novo ◽

Drug Repositioning ◽

Antiviral Drug ◽

Drug Repurposing ◽

Future Perspective

Unfortunately, to date, there is no approved specific antiviral drug treatment against COVID-19. Due to the costly and time-consuming nature of the de novo drug discovery and development process, in recent days, the computational drug repositioning method has been highly regarded for accelerating the drug-discovery process. The selection of drug target molecule(s), preparation of an approved therapeutics agent library, and in silico evaluation of their affinity to the subjected target(s) are the main steps of a molecular docking-based drug repositioning process, which is the most common computational drug re-tasking process. In this chapter, after a review on origin, pathophysiology, molecular biology, and drug development strategies against COVID-19, recent advances, challenges as well as the future perspective of molecular docking-based drug repositioning for COVID-19 are discussed. Furthermore, as a case study, the molecular docking-based drug repurposing process was planned to screen the 3CLpro inhibitor(s) among the nine Food and Drug Administration (FDA)-approved antiviral protease inhibitors. The results demonstrated that Fosamprenavir had the highest binding affinity to 3CLpro and can be considered for more in silico, in vitro, and in vivo evaluations as an effective repurposed anti-COVID-19 drug.

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Faculty Opinions recommendation of Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13357023.14726307 ◽

2011 ◽

Author(s):

Patrick Duffy

Keyword(s):

Drug Discovery ◽

In Vitro Model ◽

Vitro Model

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Recent Advances in Drug Repurposing for Parkinson’s Disease

Current Medicinal Chemistry ◽

10.2174/0929867325666180719144850 ◽

2019 ◽

Vol 26 (28) ◽

pp. 5340-5362 ◽

Cited By ~ 2

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.

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In Silico Meets In Vitro Techniques in ADMET Profiling of Drug Discovery (Part I)

Current Drug Metabolism ◽

10.2174/138920022110201126153901 ◽

2020 ◽

Vol 21 (10) ◽

pp. 745-745

Author(s):

Supratik Kar ◽

Sagnik Chatterjee

Keyword(s):

Drug Discovery ◽

In Silico ◽

In Vitro Techniques

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Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666191010144111 ◽

2019 ◽

Vol 22 (8) ◽

pp. 509-520

Author(s):

Cauê B. Scarim ◽

Chung M. Chin

Keyword(s):

Drug Discovery ◽

Chagas Disease ◽

Drug Candidates ◽

Lead Compounds ◽

New Drug ◽

Compound Libraries ◽

Screening Assays ◽

Cruzi Infection

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.

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