Editorial: Drug Repurposing.
Ontology highlight
ABSTRACT:
SUBMITTER: Pantziarka P
PROVIDER: S-EPMC6618517 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Project description:Control of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs could also trigger human cytotoxicity associated with the kidneys and liver, including the generation of reactive oxygen species. Moreover, increased incidences of fungal resistance to the classes of azoles, such as fluconazole, itraconazole, voriconazole, or posaconazole, or echinocandins, including caspofungin, anidulafungin, or micafungin, have been documented. Of note, certain azole fungicides such as propiconazole or tebuconazole that are applied to agricultural fields have the same mechanism of antifungal action as clinical azole drugs. Such long-term application of azole fungicides to crop fields provides environmental selection pressure for the emergence of pan-azole-resistant fungal strains such as Aspergillus fumigatus having TR34/L98H mutations, specifically, a 34 bp insertion into the cytochrome P450 51A (CYP51A) gene promoter region and a leucine-to-histidine substitution at codon 98 of CYP51A. Altogether, the emerging resistance of pathogens to currently available antifungal drugs and insufficiency in the discovery of new therapeutics engender the urgent need for the development of new antifungals and/or alternative therapies for effective control of fungal pathogens. We discuss the current needs for the discovery of new clinical antifungal drugs and the recent drug repurposing endeavors as alternative methods for fungal pathogen control.
| S-EPMC7697925 | biostudies-literature
Project description: Not available
| S-BSST330 | biostudies-other
Project description:BackgroundDrug repurposing has been motivated to ameliorate low probability of success in drug discovery. For the recent decade, many in silico attempts have received primary attention as a first step to alleviate the high cost and longevity. Such study has taken benefits of abundance, variety, and easy accessibility of pharmaceutical and biomedical data. Utilizing the research friendly environment, in this study, we propose a network-based machine learning algorithm for drug repurposing. Particularly, we show a framework on how to construct a drug network, and how to strengthen the network by employing multiple/heterogeneous types of data.ResultsThe proposed method consists of three steps. First, we construct a drug network from drug-target protein information. Then, the drug network is reinforced by utilizing drug-drug interaction knowledge on bioactivity and/or medication from literature databases. Through the enhancement, the number of connected nodes and the number of edges between them become more abundant and informative, which can lead to a higher probability of success of in silico drug repurposing. The enhanced network recommends candidate drugs for repurposing through drug scoring. The scoring process utilizes graph-based semi-supervised learning to determine the priority of recommendations.ConclusionsThe drug network is reinforced in terms of the coverage and connections of drugs: the drug coverage increases from 4738 to 5442, and the drug-drug associations as well from 808,752 to 982,361. Along with the network enhancement, drug recommendation becomes more reliable: AUC of 0.89 was achieved lifted from 0.79. For typical cases, 11 recommended drugs were shown for vascular dementia: amantadine, conotoxin GV, tenocyclidine, cycloeucine, etc.
| S-EPMC6651901 | biostudies-literature
Project description:The study analyses the effect of multiple drugs on transcriptomic profile of Drosophila melanogaster. At the end of treatment, the head tissues were collected and homogenized in trizol for RNA extraction. The transcriptomic profiling was done using Affymetrix Drosophila Genome 2.0 array.
2022-12-01 | GSE142384 | GEO
Project description:In the area of drug discovery, repurposing strategies represent an approach to discover new uses of approved drugs besides their original indications. We used this approach to investigate the effects of dimethyl fumarate (DMF), a drug approved for relapsing-remitting multiple sclerosis and psoriasis treatment, on early injury associated with diabetic retinopathy (DR). We used an in vivo streptozotocin (STZ)-induced diabetic rat model. Diabetes was induced by a single injection of STZ in rats, and after 1 week, a group of animals was treated with a daily intraperitoneal injection of DMF or a vehicle. Three weeks after diabetes induction, the retinal expression levels of key enzymes involved in DR were evaluated. In particular, the biomarkers COX-2, iNOS, and HO-1 were assessed via Western blot and immunohistochemistry analysis. Diabetic rats showed a significant retinal upregulation of COX-2 and iNOS compared to the retina of normal rats (non-diabetic), and an increase in HO-1 was also observed in the STZ group. This latter result was due to a mechanism of protection elicited by the pathological condition. DMF treatment significantly induced the retinal expression of HO-1 in STZ-induced diabetic animals with a reduction in iNOS and COX-2 retinal levels. Taken together, these results suggested that DMF might be useful to counteract the inflammatory process and the oxidative response in DR. In conclusion, we believe that DMF represents a potential candidate to treat diabetic retinopathy and warrants further in vivo and clinical evaluation.
| S-EPMC10386358 | biostudies-literature
Project description:COVID-19 has now been declared a pandemic and new treatments are urgently needed as we enter a phase beyond containment. Developing new drugs from scratch is a lengthy process, thus impractical to face the immediate global challenge. Drug repurposing is an emerging strategy where existing medicines, having already been tested safe in humans, are redeployed to combat difficult-to-treat diseases. While using such repurposed drugs individually may ultimately not yield a significant clinical benefit, carefully combined cocktails could be very effective, as was for HIV in the 1990s; the urgent question now being which combination.
| S-EPMC7117595 | biostudies-literature
Project description:Despite significant treatment advances over the past decade, metastatic gastrointestinal stromal tumor (GIST) remains largely incurable. Rare diseases, such as GIST, individually affect small groups of patients but collectively are estimated to affect 25 to 30 million people in the United States alone. Given the costs associated with the discovery, development, and registration of new drugs, orphan diseases such as GIST are often not pursued by mainstream pharmaceutical companies. As a result, "drug repurposing" or "repositioning," has emerged as an alternative to the traditional drug development process. In this study, we screened 796 U.S. Food and Drug Administration (FDA)-approved drugs and found that two of these compounds, auranofin (Ridaura) and fludarabine phosphate, effectively and selectively inhibited the proliferation of GISTs, including imatinib-resistant cells. One of the most notable drug hits, auranofin, an oral, gold-containing agent approved by the FDA in 1985 for the treatment of rheumatoid arthritis, was found to inhibit thioredoxin reductase activity and induce reactive oxygen species (ROS) production, leading to dramatic inhibition of GIST cell growth and viability. Importantly, the anticancer activity associated with auranofin was independent of imatinib-resistant status, but was closely related to the endogenous and inducible levels of ROS. Coupled with the fact that auranofin has an established safety profile in patients, these findings suggest for the first time that auranofin may have clinical benefit for patients with GIST, particularly in those suffering from imatinib-resistant and recurrent forms of this disease.
| S-EPMC3707936 | biostudies-literature
Project description: Not available
| S-EPMC10581586 | biostudies-literature
Project description:Sepsis involves life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite three decades of efforts and multiple clinical trials, no treatment, except antibiotics and supportive care, has been approved for this devastating syndrome. Simultaneously, numerous preclinical studies have shown the effectiveness of oncology-indicated drugs in ameliorating sepsis. Here we focus on cataloging these efforts with both oncology-approved and under-development drugs that have been repositioned to treat bacterial-induced sepsis models. In this context, we also envision the exciting prospect for further standard and oncology drug combination testing that could ultimately improve clinical outcomes in sepsis.
| S-EPMC9030585 | biostudies-literature
Project description:We have conducted a bibliometric review of drug repurposing by scanning >25 million papers in PubMed and using text-mining methods to gather, count and analyze chemical-disease therapeutic relationships. We find that >60% of the ∼35,000 drugs or drug candidates identified in our study have been tried in more than one disease, including 189 drugs that have been tried in >300 diseases each. Whereas in the majority of cases these drugs were applied in therapeutic areas close to their original use, there have been striking, and perhaps instructive, successful attempts of drug repurposing for unexpected, novel therapeutic areas.
| S-EPMC5963941 | biostudies-literature