Prospective Anti-cancer Agents: A Recent Update on Drug Repurposing

Background: The drug discovery phases traditionally involve target identification as well as lead optimization through high throughput screening, which is usually time-consuming with a higher risk failure. In the case of new anticancer drugs, drug accessibility remains a great challenge due to high pricing which usually leads to a huge economic burden on a cancer patient. Objective and Methods: Drug repurposing appears to be a better alternative method for drug development. Repurposing with many benefits as faster, cheaper, safer, and easier has become the most sought research strategy nowadays. Large numbers of approved drug are now being studied for cancer. In present review, we furnish recent updates on the field of repurposing especially about prospective anti-cancer agents including selected examples of potent phytochemicals from various authentic databases. Results: We have also detailed the current approaches utilized for repurposing along with the clinical status of the repurposed drug. Conclusion: Drug repurposing has potential and scope for reducing the cost of drug discovery in the oncology field.

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Use of Genomics in Drug Discovery: Application to Target Identification, High-Throughput Screening and Diagnosis

Journal of Pesticide Science ◽

10.1584/jpestics.26.305 ◽

2001 ◽

Vol 26 (3) ◽

pp. 305-308 ◽

Cited By ~ 1

Author(s):

Hisafumi YAMADA-OKABE

Keyword(s):

Drug Discovery ◽

High Throughput ◽

High Throughput Screening ◽

Target Identification ◽

Screening And Diagnosis

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Drug Repurposing: A Paradigm Shift in Drug Discovery

International Journal of Applied Pharmaceutical Sciences and Research ◽

10.21477/ijapsr.5.4.2 ◽

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.

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Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery

10.1101/2020.08.02.233064 ◽

2020 ◽

Author(s):

Michael F. Cuccarese ◽

Berton A. Earnshaw ◽

Katie Heiser ◽

Ben Fogelson ◽

Chadwick T. Davis ◽

...

Keyword(s):

Deep Learning ◽

Drug Discovery ◽

High Throughput Screening ◽

Drug Repurposing ◽

Rapid Identification ◽

Large Molecules ◽

Tnf Α ◽

Genetic Perturbations ◽

Compound Screening ◽

Model Drug

ABSTRACTDevelopment of accurate disease models and discovery of immune-modulating drugs is challenged by the immune system’s highly interconnected and context-dependent nature. Here we apply deep-learning-driven analysis of cellular morphology to develop a scalable “phenomics” platform and demonstrate its ability to identify dose-dependent, high-dimensional relationships among and between immunomodulators, toxins, pathogens, genetic perturbations, and small and large molecules at scale. High-throughput screening on this platform demonstrates rapid identification and triage of hits for TGF-β- and TNF-α-driven phenotypes. We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. The presented library of images, deep learning features, and compound screening data from immune profiling and COVID-19 screens serves as a deep resource for immune biology and cellular-model drug discovery with immediate impact on the COVID-19 pandemic.

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

Current Molecular Medicine ◽

10.2174/1566524020666200619125404 ◽

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.

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Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

Pharmaceuticals ◽

10.3390/ph13010008 ◽

2020 ◽

Vol 13 (1) ◽

pp. 8 ◽

Cited By ~ 17

Author(s):

Eavan C. McLoughlin ◽

Niamh M. O’Boyle

Keyword(s):

Binding Site ◽

High Throughput Screening ◽

Drug Targets ◽

Rational Design ◽

Clinical Status ◽

Cancer Therapies ◽

Colchicine Binding Site ◽

Anti Cancer ◽

Recent Developments ◽

Important Drug

It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments.

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An overview of drug discovery and development

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0307 ◽

2020 ◽

Vol 12 (10) ◽

pp. 939-947 ◽

Cited By ~ 2

Author(s):

Nurken Berdigaliyev ◽

Mohamad Aljofan

Keyword(s):

Drug Discovery ◽

High Throughput ◽

Combinatorial Chemistry ◽

New Technologies ◽

Drug Repurposing ◽

Drug Discovery And Development ◽

Advantages And Disadvantages ◽

High Throughput Drug Screening ◽

The Cost ◽

Early Drug

A new medicine will take an average of 10–15 years and more than US$2 billion before it can reach the pharmacy shelf. Traditionally, drug discovery relied on natural products as the main source of new drug entities, but was later shifted toward high-throughput synthesis and combinatorial chemistry-based development. New technologies such as ultra-high-throughput drug screening and artificial intelligence are being heavily employed to reduce the cost and the time of early drug discovery, but they remain relatively unchanged. However, are there other potentially faster and cheaper means of drug discovery? Is drug repurposing a viable alternative? In this review, we discuss the different means of drug discovery including their advantages and disadvantages.

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Prospects for repurposing CNS drugs for cancer treatment

Oncology Reviews ◽

10.4081/oncol.2019.411 ◽

2019 ◽

Vol 13 (1) ◽

Cited By ~ 7

Author(s):

Mohamed Abdelaleem ◽

Hossam Ezzat ◽

Muhammed Osama ◽

Adel Megahed ◽

Waleed Alaa ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Drug Repurposing ◽

New Approach ◽

Central Nervous System Drugs ◽

Anti Cancer ◽

Cns Drugs ◽

New Anticancer Drugs

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drugs over the last 8 years period (2010-2018) and including only evidence from Q1 journals as indicated by Scimago website (www.scimagojr.com). We concluded that Some Central Nervous system drugs show a great potential as anti-cancer in vitro, in vivo and clinical trials through different mechanisms and pathways in different types of cancer that reveal a promising evidence for the repurposing of CNS drugs for new indications.

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Statistical models for identifying frequent hitters in high throughput screening

Scientific Reports ◽

10.1038/s41598-020-74139-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Samuel Goodwin ◽

Golnaz Shahtahmassebi ◽

Quentin S. Hanley

Keyword(s):

Drug Discovery ◽

High Throughput ◽

High Throughput Screening ◽

Negative Binomial ◽

Data Sets ◽

Individual Compound ◽

Data Set ◽

Binomial Distributions ◽

Compound Libraries ◽

Large Numbers

Abstract High throughput screening (HTS) interrogates compound libraries to find those that are “active” in an assay. To better understand compound behavior in HTS, we assessed an existing binomial survivor function (BSF) model of “frequent hitters” using 872 publicly available HTS data sets. We found large numbers of “infrequent hitters” using this model leading us to reject the BSF for identifying “frequent hitters.” As alternatives, we investigated generalized logistic, gamma, and negative binomial distributions as models for compound behavior. The gamma model reduced the proportion of both frequent and infrequent hitters relative to the BSF. Within this data set, conclusions about individual compound behavior were limited by the number of times individual compounds were tested (1–1613 times) and disproportionate testing of some compounds. Specifically, most tests (78%) were on a 309,847-compound subset (17.6% of compounds) each tested ≥ 300 times. We concluded that the disproportionate retesting of some compounds represents compound repurposing at scale rather than drug discovery. The approach to drug discovery represented by these 872 data sets characterizes the assays well by challenging them with many compounds while each compound is characterized poorly with a single assay. Aggregating the testing information from each compound across the multiple screens yielded a continuum with no clear boundary between normal and frequent hitting compounds.

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Anti-cancer potential of some commonly used drugs

Current Pharmaceutical Design ◽

10.2174/1381612827666210622104821 ◽

2021 ◽

Vol 27 ◽

Author(s):

Shweta Dang ◽

Pallavi Kumari

Keyword(s):

Clinical Trials ◽

Drug Discovery ◽

Drug Repurposing ◽

Cancer Therapeutics ◽

In Vivo Studies ◽

New Drug ◽

Area Of Interest ◽

Therapeutic Benefits ◽

Anti Cancer

: Cancer is a global concern leading to millions of deaths every year. A declining trend in new drug discovery and development is becoming one of the major issues among the pharmaceutical, biotechnology industries, and regulatory agencies. New drug development is proven to be a very lengthy and costly process. The launch of a new drug takes 8-12 years and huge investments. The success rate in oncology therapeutics is also low due to toxicities at the pre-clinical and clinical trial levels. Many oncological drugs get rejected at a very promising stage, showing adverse reactions on healthy cells. Thus, exploring new therapeutic benefits of the existing, shelved drugs for their anti-cancerous action could result in a therapeutic approach preventing the toxicities which occur during clinical trials. Drug repurposing has the potential to overcome the challenges faced via conventional way of drug discovery and is becoming an area of interest for researchers and scientists. However, very few in vivo studies are conducted to prove the anti-cancerous activity of the drugs. Insufficient in vivo animal studies and a lack of human clinical trials are the lacunae in the field of drug repurposing. This review focuses on an aspect of drug repurposing for cancer therapeutics. Various studies that show that drugs approved for clinical indications other than cancer have shown promising anti-cancer activities. Some of the commonly used drugs like Benzodiazepines (Diazepam, Midzolam), Antidepressants (Imipramine, Clomipramine, and Citalopram), Antiepileptic (Valporic acid, Phenytoin), Antidiabetics (metformin), etc. have been reported to show potential activity against the cancerous cells.

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