scholarly journals Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System

2020 ◽  
Vol 21 (14) ◽  
pp. 4957 ◽  
Author(s):  
Federica Laudisi ◽  
Martin Marônek ◽  
Antonio Di Grazia ◽  
Giovanni Monteleone ◽  
Carmine Stolfi
Keyword(s):  
Digestive System ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
The Body ◽  
Attrition Rates ◽  
Anti Cancer ◽  
Approved Drugs ◽  
Parasitic Worms ◽  
Effective Drugs ◽  
Anthelmintic Drugs

Tumors of the digestive system, when combined together, account for more new cases and deaths per year than tumors arising in any other system of the body and their incidence continues to increase. Despite major efforts aimed at discovering and validating novel and effective drugs against these malignancies, the process of developing such drugs remains lengthy and costly, with high attrition rates. Drug repositioning (also known as drug repurposing), that is, the process of finding new uses for approved drugs, has been gaining popularity in oncological drug development as it provides the opportunity to expedite promising anti-cancer agents into clinical trials. Among the drugs considered for repurposing in oncology, compounds belonging to some classes of anthelmintics—a group of agents acting against infections caused by parasitic worms (helminths) that colonize the mammalian intestine—have shown pronounced anti-tumor activities and attracted particular attention due to their ability to target key oncogenic signal transduction pathways. In this review, we summarize and discuss the available experimental and clinical evidence about the use of anthelmintic drugs for the treatment of cancers of the digestive system.

scholarly journals Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3193
Author(s):  
Christina Pfab ◽  
Luisa Schnobrich ◽  
Samir Eldnasoury ◽  
André Gessner ◽  
Nahed El-Najjar
Keyword(s):  
Clinical Trials ◽  
Antimicrobial Agents ◽  
Large Body ◽  
Drug Repurposing ◽  
Extensive Discussion ◽  
Attrition Rates ◽  
Beneficial Effects ◽  
Stage Of Development ◽  
Development Costs ◽  
Approved Drugs

The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.

scholarly journals Natural Products Extracted from Fungal Species as New Potential Anti-Cancer Drugs: A Structure-Based Drug Repurposing Approach Targeting HDAC7

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5524
Author(s):  
Annalisa Maruca ◽  
Roberta Rocca ◽  
Raffaella Catalano ◽  
Francesco Mesiti ◽  
Giosuè Costa ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Ibotenic Acid ◽  
Fungal Species ◽  
Anticancer Compounds ◽  
Chemical Database ◽  
Starting Point ◽  
Anti Cancer ◽  
Mcf 7

Mushrooms can be considered a valuable source of natural bioactive compounds with potential polypharmacological effects due to their proven antimicrobial, antiviral, antitumor, and antioxidant activities. In order to identify new potential anticancer compounds, an in-house chemical database of molecules extracted from both edible and non-edible fungal species was employed in a virtual screening against the isoform 7 of the Histone deacetylase (HDAC). This target is known to be implicated in different cancer processes, and in particular in both breast and ovarian tumors. In this work, we proposed the ibotenic acid as lead compound for the development of novel HDAC7 inhibitors, due to its antiproliferative activity in human breast cancer cells (MCF-7). These promising results represent the starting point for the discovery and the optimization of new HDAC7 inhibitors and highlight the interesting opportunity to apply the “drug repositioning” paradigm also to natural compounds deriving from mushrooms.

scholarly journals Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hongbo Shen ◽  
Feifei Wang ◽  
Gucheng Zeng ◽  
Ling Shen ◽  
Han Cheng ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Proof Of Concept ◽  
Intracellular Replication ◽  
Anti Cancer ◽  
Mdr Tb ◽  
Approved Drugs ◽  
Effective Drugs ◽  
Slow Growing

Abstract While there is an urgent need to develop new and effective drugs for treatment of tuberculosis (TB) and multi-drug resistant TB (MDR-TB), repurposing FDA (U.S. Food and Drug Administration) -approved drugs for development of anti-TB agents may decrease time and effort from bench to bedside. Here, we employed host cell-based high throughput screening (HTS) assay to screen and characterize FDA-approved, off-patent library drugs for anti-Mycobacterium tuberculosis (MTB) activities. The cell-based HTS allowed us to identify an anti-cancer drug of bis-biguanide dihydrochloride (BBD) as potent anti-mycobacteria agent. Further characterization showed that BBD could inhibit intracellular and extracellular growth of M. smegmatis and slow-growing M. bovis BCG. BBD also potently inhibited replication of clinically-isolated MTB and MDR-TB strains. The proof-of-concept study showed that BBD treatment of MTB-infected mice could significantly decrease CFU counts in the lung and spleen. Notably, comparative evaluation showed that MTB CFU counts in BBD-treated mice were lower than those in rifampicin-treated mice. No apparent BBD side effects were found in BBD-treated mice. Thus, our findings support further studies to develop BBD as a new and effective drug against TB and MDR-TB.

scholarly journals Drug REpurposing using AI/ML tools - for Rare Diseases (DREAM-RD): A case study with Fragile X Syndrome (FXS)

2020 ◽  
Author(s):  
Kavitha Agastheeswaramoorthy ◽  
Aarti Sevilimedu
Keyword(s):  
Fragile X Syndrome ◽  
Drug Repositioning ◽  
Fragile X ◽  
Drug Repurposing ◽  
Machine Learning Algorithms ◽  
Specific Gene ◽  
Drug Induced ◽  
Approved Drugs ◽  
Disease Specific

AbstractDrug repositioning is emerging as an increasingly relevant option for rare disease therapy and management. Various methods for identifying suitable drug candidates have been tried and range from clinical symptomatic repurposing to data driven strategies which are based on the disease-specific gene or protein expression, modification, signalling and physiological perturbation profiles. The use of Artificial Intelligence (AI) and machine learning algorithms (ML) allows one to combine diverse data sets, and extract disease-specific data profiles which may not be intuitive or apparent from a subset of data. In this case study with Fragile X syndrome and autism, we have used multiple computational methodologies to extract profiles, which are then combined to arrive at a comprehensive signature (disease DEG). This DEG was then used to interrogate the large collection of drug-induced perturbation profiles present in public databases, to find appropriate small molecules to reverse or mimic the disease-profiles. We have labelled this pipeline Drug Repurposing using AI/ML tools - for Rare Diseases (DREAM-RD). We have shortlisted over 100 FDA approved drugs using the aforementioned pipeline, which may potentially be useful to ameliorate autistic phenotypes associated with FXS.

scholarly journals Computational guided approach for drug repurposing against SARS-CoV-2

2021 ◽  
Author(s):  
Jigisha Anand ◽  
Tanmay Ghildiyal ◽  
Aakanksha Madhwal ◽  
Rishabh Bhatt ◽  
Devvret Verma ◽  
...  
Keyword(s):  
Drug Targets ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Computational Docking ◽  
Drug Candidates ◽  
Docking Tool ◽  
Inhibitory Potential ◽  
Approved Drugs ◽  
Tract Infections

Background: In the current SARS-CoV-2 outbreak, drug repositioning emerges as a promising approach to develop efficient therapeutics in comparison to de novo drug development. The present investigation screened 130 US FDA-approved drugs including hypertension, cardiovascular diseases, respiratory tract infections (RTI), antibiotics and antiviral drugs for their inhibitory potential against SARS-CoV-2. Materials & methods: The molecular drug targets against SARS-CoV-2 proteins were determined by the iGEMDOCK computational docking tool. The protein homology models were generated through SWISS Model workspace. The pharmacokinetics of all the ligands was determined by ADMET analysis. Results: The study identified 15 potent drugs exhibiting significant inhibitory potential against SARS-CoV-2. Conclusion: Our investigation has identified possible repurposed drug candidates to improve the current modus operandi of the treatment given to COVID-19 patients.

scholarly journals In silico drug repurposing of anticancer drug 5-FU and analogues against SARS-CoV-2 main protease

2021 ◽  
Author(s):  
Aristote Matondo ◽  
Washington Dendera ◽  
Bienfait K. Isamura ◽  
Koto-te-Nyiwa Ngbolua ◽  
Hilaire V.S. Mambo ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Pharmacological Action ◽  
Time Saving ◽  
Therapeutic Uses ◽  
Main Protease ◽  
Approved Drugs ◽  
Effective Drugs ◽  
Therapeutic Profile

The pressing need to find effective drugs against the current deadly COVID-19 disease has recently motivated numerous studies using different approaches to address the problem. One time-saving and less costly strategy is the drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following the same trend, this study has investigated the potential inhibitory activity of 5-FU and its analogues against the SARS-CoV-2 main protease as well as their profile of druggability using molecular docking and ADMET methods. From the calculations performed, four candidates showed promising results with respect to the binding affinity to the target protease, 3CLpro, the therapeutic profile of druggability and safety. Further in-vitro and in-vivo investigations are needed that may clarify their possible mechanism of the pharmacological action to combat COVID-19.

scholarly journals Drug Repurposing: A Review

2021 ◽  
pp. 161-169
Author(s):  
Rani Teksinh Bhagat ◽  
Santosh Ramarao Butle
Keyword(s):  
Drug Development ◽  
Research And Development ◽  
Development Process ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
New Drugs ◽  
Preclinical Development ◽  
Therapeutic Uses ◽  
Original Application ◽  
Approved Drugs

The drug development is a very time consuming and complex process. Drug development Process is Expensive. Success rate for the new drug development is very small. In recent years, decreases the new drugs development. The powerful tools are developed to support the research and development (R&D) process is essential. The Drug repurposing are helpful for research and development process. The drug re-purposing as an approach finds new therapeutic uses for current candidates or existing candidates or approved drugs, different from its original application. The main aimed of Drug repurposing is to reduce costs and research time investments in Research & Development. It is used for the diagnosis and treatment of various diseases. Repositioning is important over traditional approaches and need for effective therapies. Drug re-purposing identifies new application for already banned or existing drugs from market. In drug design, drug repurposing plays important role, because it helps to preclinical development. It reducing time efforts, expenses and failures in drug discovery process. It is also called as drug repositioning, drug redirecting, drug reprofiling.

scholarly journals In-Silico FDA-Approved Drug Repurposing to Find the Possible Treatment of Coronavirus Disease-19 (COVID-19)

2020 ◽  
Author(s):  
Kumar Sharp ◽  
Dr. Shubhangi Dange
Keyword(s):  
In Silico ◽  
Drug Target ◽  
Drug Repurposing ◽  
Target Interaction ◽  
Compound Libraries ◽  
Anti Cancer ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Large Compound ◽  
Better Than

Identification of potential drug-target interaction for approved drugs serves as the basis of repurposing drugs. Studies have shown polypharmacology as common phenomenon. In-silico approaches help in screening large compound libraries at once which could take years in a laboratory. We screened a library of 1050 FDA-approved drugs against spike glycoprotein of SARS-CoV2 in-silico. Anti-cancer drugs have shown good binding affinity which is much better than hydroxychloroquine and arbidol. We have also introduced a hypothesis named “Bump” hypothesis which and be developed further in field of computational biology.

scholarly journals In-Silico FDA-Approved Drug Repurposing to Find the Possible Treatment of Coronavirus Disease-19 (COVID-19)

2020 ◽  
Author(s):  
Kumar Sharp ◽  
Dr. Shubhangi Dange
Keyword(s):  
In Silico ◽  
Drug Target ◽  
Drug Repurposing ◽  
Target Interaction ◽  
Compound Libraries ◽  
Anti Cancer ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Large Compound ◽  
Better Than

Identification of potential drug-target interaction for approved drugs serves as the basis of repurposing drugs. Studies have shown polypharmacology as common phenomenon. In-silico approaches help in screening large compound libraries at once which could take years in a laboratory. We screened a library of 1050 FDA-approved drugs against spike glycoprotein of SARS-CoV2 in-silico. Anti-cancer drugs have shown good binding affinity which is much better than hydroxychloroquine and arbidol. We have also introduced a hypothesis named “Bump” hypothesis which and be developed further in field of computational biology.

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