Готові списки джерел за темами / Repurposed drug

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Добірка наукової літератури з теми "Repurposed drug"

Автор: Grafiati
Опубліковано: 12 квітня 2025

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Статті в журналах з теми "Repurposed drug"

1

Al Khzem, Abdulaziz H., Mohamed S. Gomaa, Mansour S. Alturki, Nada Tawfeeq, Mohammad Sarafroz, Shareefa M. Alonaizi, Alhassan Al Faran, Laela Ahmed Alrumaihi, Fatimah Ahmed Alansari, and Abdullah Abbas Alghamdi. "Drug Repurposing for Cancer Treatment: A Comprehensive Review." International Journal of Molecular Sciences 25, no. 22 (November 19, 2024): 12441. http://dx.doi.org/10.3390/ijms252212441.

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Анотація:
Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therapeutic area where drug repurposing has shown the most prominent impact. This review presents a compilation of medications that have been repurposed for the treatment of various types of cancers. It describes the initial therapeutic and pharmacological classes of the repurposed drugs and their new applications and mechanisms of action in cancer treatment. The review reports on drugs from various pharmacological classes that have been successfully repurposed for cancer treatment, including approved ones and those in clinical trials and preclinical development. It stratifies drugs based on their anticancer repurpose as multi-type, type-specific, and mechanism-directed, and according to their pharmacological classes. The review also reflects on the future potential that drug repurposing has in the clinical development of novel anticancer therapies.
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2

Aleksic, Sandra. "REPURPOSED FOR AGING." Innovation in Aging 8, Supplement_1 (December 2024): 139–40. https://doi.org/10.1093/geroni/igae098.0449.

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Abstract Chronic diseases represent the leading driver of health care cost, with detrimental impact on function, independence, and quality of life in the aging society. Geroscience-guided approaches seek to target aging biology to extend healthspan, defined as the period of life spent without major disease and disability. Repurposing Food and Drug Administration (FDA) - approved drugs as gerotherapeutics (geroscience-guided pharmacologic interventions) offers the advantage of known pharmacologic profile and existing clinical experience and can represent a cost-effective strategy to test interventions for extension of healthspan. Among FDA-approved drugs, candidates with geroscience potential can be identified based on the evidence of extension of healthspan and lifespan in model organisms coupled with clinical evidence of benefits extending beyond the diseases targeted by the drug, through mechanisms that involve modulation of hallmarks of aging. Given the inseparable connections between metabolism and aging, it is not surprising that several FDA-approved drugs developed for treatment of metabolic dysfunction are emerging as potential gerotherapeutics. Metformin (discussed by Dr. Sara Espinoza), a widely used oral antidiabetic drug, extends lifespan in preclinical models, while observational clinical evidence supports its role in prevention of several chronic diseases. Two newer antidiabetic drug classes, glucagon-like peptide 1 (GLP1) receptor agonists (discussed by Dr. John Newman) and sodium- glucose cotransporter 2 (SGLT2) inhibitors (discussed by Dr. Carolina Solis-Herrera), have demonstrated healthspan and lifespan benefits above and beyond treatment of diabetes. Emerging evidence for modulation of multiple hallmarks of aging supports gerotherapeutic properties of these drugs. Clinical trials targeting several aging-relevant outcomes are underway.
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Araújo, Diana, Eduarda Ribeiro, Irina Amorim, and Nuno Vale. "Repurposed Drugs in Gastric Cancer." Molecules 28, no. 1 (December 30, 2022): 319. http://dx.doi.org/10.3390/molecules28010319.

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Анотація:
Gastric cancer (GC) is one of the major causes of death worldwide, ranking as the fifth most incident cancer in 2020 and the fourth leading cause of cancer mortality. The majority of GC patients are in an advanced stage at the time of diagnosis, presenting a poor prognosis and outcome. Current GC treatment approaches involve endoscopic detection, gastrectomy and chemotherapy or chemoradiotherapy in an adjuvant or neoadjuvant setting. Drug development approaches demand extreme effort to identify molecular mechanisms of action of new drug candidates. Drug repurposing is based on the research of new therapeutic indications of drugs approved for other pathologies. In this review, we explore GC and the different drugs repurposed for this disease.
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4

Olgen, Sureyya, and Lakshmi P. Kotra. "Drug Repurposing in the Development of Anticancer Agents." Current Medicinal Chemistry 26, no. 28 (October 25, 2019): 5410–27. http://dx.doi.org/10.2174/0929867325666180713155702.

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Background: Research into repositioning known drugs to treat cancer other than the originally intended disease continues to grow and develop, encouraged in part, by several recent success stories. Many of the studies in this article are geared towards repurposing generic drugs because additional clinical trials are relatively easy to perform and the drug safety profiles have previously been established. Objective: This review provides an overview of anticancer drug development strategies which is one of the important areas of drug restructuring. Methods: Repurposed drugs for cancer treatments are classified by their pharmacological effects. The successes and failures of important repurposed drugs as anticancer agents are evaluated in this review. Results and Conclusion: Drugs could have many off-target effects, and can be intelligently repurposed if the off-target effects can be employed for therapeutic purposes. In cancer, due to the heterogeneity of the disease, often targets are quite diverse, hence a number of already known drugs that interfere with these targets could be deployed or repurposed with appropriate research and development.
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Moura, Catarina, Ana Salomé Correia, Mariana Pereira, Eduarda Ribeiro, Joana Santos, and Nuno Vale. "Atorvastatin and Nitrofurantoin Repurposed in the Context of Breast Cancer and Neuroblastoma Cells." Biomedicines 11, no. 3 (March 15, 2023): 903. http://dx.doi.org/10.3390/biomedicines11030903.

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Chemotherapy still plays a central role in the treatment of cancer. However, it is often accompanied by off-target effects that result in severe side-effects and development of drug resistance. The aim of this work was to study the efficacy of different repurposed drugs on the viability of MCF-7 and SH-SY5Y breast cancer and neuroblastoma cells, respectively. In addition, combinations of these repurposed drugs with a classical chemotherapeutic drug (doxorubicin) were also carried out. The cytotoxic effects of the repurposed drugs were evaluated individually and in combination in both cancer cell lines, assessed by MTT assays and morphological evaluation of the cells. The results demonstrated that atorvastatin reduced the viability of both cell lines. However, nitrofurantoin was able to induce cytotoxic effects in MCF-7 cells, but not in SH-SY5Y cells. The combinations of the repurposed drugs with doxorubicin induced a higher inhibition on cell viability than the repurposed drugs individually. The combination of the two repurposed drugs demonstrated that they potentiate each other. Synergism studies revealed that the combination of doxorubicin with the two repurposed drugs was more effective in SH-SY5Y cells, compared to MCF-7 cells. Taken together, our preliminary study highlights the potential use of atorvastatin and nitrofurantoin in the context of breast cancer and neuroblastoma.
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Prosdocimi, Marco, Cristina Zuccato, Lucia Carmela Cosenza, Monica Borgatti, Ilaria Lampronti, Alessia Finotti та Roberto Gambari. "A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs". Wellcome Open Research 7 (23 червня 2022): 150. http://dx.doi.org/10.12688/wellcomeopenres.17845.2.

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Анотація:
Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', ‘drug rescue’, ‘drug re-tasking’ and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the “off-label” use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial.
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Prosdocimi, Marco, Cristina Zuccato, Lucia Carmela Cosenza, Monica Borgatti, Ilaria Lampronti, Alessia Finotti та Roberto Gambari. "A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs". Wellcome Open Research 7 (17 серпня 2022): 150. http://dx.doi.org/10.12688/wellcomeopenres.17845.3.

Повний текст джерела
Анотація:
Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', ‘drug rescue’, ‘drug re-tasking’ and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the “off-label” use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial.
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8

Prosdocimi, Marco, Cristina Zuccato, Lucia Carmela Cosenza, Monica Borgatti, Ilaria Lampronti, Alessia Finotti та Roberto Gambari. "A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs". Wellcome Open Research 7 (12 травня 2022): 150. http://dx.doi.org/10.12688/wellcomeopenres.17845.1.

Повний текст джерела
Анотація:
Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', ‘drug rescue’, ‘drug re-tasking’ and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the “off-label” use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial.
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9

Stone, Heather, Mili Duggal, Leonard Sacks, and Mayurika Ghosh. "1380. Safety of Repurposed Drugs for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: An Analysis of Adverse Events Reported in the Literature." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S501. http://dx.doi.org/10.1093/ofid/ofz360.1244.

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Abstract Background Multi and extensively drug-resistant (MDR and XDR) tuberculosis (TB) remains a treatment challenge due to drug adverse events (AEs) and long regimens. Our aim was to identify AEs which resulted from repurposing drugs for MDR and XDR-TB. Methods A PubMed search for case reports of repurposed drugs for MDR and XDR-TB from January 1, 2014 to October 23, 2018 identified 130 patients (78 MDR, 52 XDR) in 91 articles. There were 31 extrapulmonary, 81 pulmonary TB cases, and 18 with both. Drugs were regarded as repurposed if they were either not approved for TB by the FDA, or they were approved for TB but were used in novel populations, novel combinations, or nonstandard doses. Drug labels were reviewed for AEs. Results Linezolid (n = 65) and moxifloxacin (n = 48) were the most commonly repurposed drugs. The following were also frequently used: clofazimine (n = 47), levofloxacin (n = 45), amikacin (n = 43), amoxicillin-clavulanate (n = 40), kanamycin (n = 36), carbapenems (n = 22), and clarithromycin (n = 17). Of the drugs that are approved for TB, the following were repurposed in a novel population, dose, or combination: cycloserine (n = 20), bedaquiline (n = 13), capreomycin (n = 4), ethambutol (n = 3), and isoniazid (n = 3). Treatments were discontinued due to AEs in 41 patients. There were no discontinuations for amoxicillin-clavulanate and levofloxacin. Extended drug exposure is a unique treatment feature for MDR and XDR-TB, which often requires ~2 years of treatment. Approximately 87% of treatment discontinuations due to AEs occurred after >1 month of exposure. AEs leading to treatment discontinuation after > 6 months of drug exposure were seen in 15 cases, of which 12 were due to linezolid and cycloserine. Peripheral and optic neuropathy was the most common AE reported (linezolid n = 12, cycloserine n = 1). Most AEs were labeled events. Conclusion Several antimicrobials are being repurposed to treat MDR and XDR-TB. There were no AEs reported after prolonged use that was not described in drug labels. Physicians should review information in labeling if prescribing drugs in this manner. There is a need for comparative safety data for repurposed drugs assessed through clinical trials. Disclosures All authors: No reported disclosures.
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Jayaram, Saravanan, Emdormi Rymbai, Deepa Sugumar, and Divakar Selvaraj. "Drug Repurposing: A Paradigm Shift in Drug Discovery." INTERNATIONAL JOURNAL OF APPLIED PHARMACEUTICAL SCIENCES AND RESEARCH 5, no. 04 (June 30, 2020): 60–68. http://dx.doi.org/10.21477/ijapsr.5.4.2.

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Анотація:
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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Більше джерел

Дисертації з теми "Repurposed drug"

1

Olayanju, Olatunde. "Efficacy and safety of novel and repurposed drugs for the treatment of drug-resistant tuberculosis." Doctoral thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32322.

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Background: There is widespread concern about the rise of drug-resistant TB because treatment outcomes of affected patients remain poor and treatment options are limited. After more than a forty-year gap without any breakthrough discovery, several new (bedaquiline and delamanid) and repurposed drugs (linezolid) are increasingly becoming available for use. However, data regarding the efficacy and safety of these drugs in drug-resistant TB patients, with or without HIV infection, from a real-life programmatic setting are lacking. This thesis aims to address that knowledge gap and provide information for management of drug-resistant TB in countries with high disease burden. Methods: A total of 326 drug resistant TB patients were prospectively followed up between January 2008 and April 2018. The efficacy and safety of two new drugs (bedaquiline and delamanid) and one repurposed drug (linezolid) was determined in these patients in three studies. In the first study, 24 months treatment outcomes and adverse event profiles were compared between extensively drug resistant (XDR) TB patients who received programmatic treatment regimens with the backbone of second line injectables and fluoroquinolones (nonbedaquiline-based) and those who received a bedaquiline- and/ or linezolid-based treatment regimen. The second study determined the frequency of system-specific adverse events associated with linezolid. The third study interrogated the safety and effectiveness of a strengthened treatment regimen containing a combination of delamanid and bedaquiline in patients with poor prognostic features compared to bedaquiline-based regimen. Results: In the first study, patients who received a bedaquiline-based treatment regimen had a significantly greater favourable outcome rate (66.2% vs 13.2%; p<0.001) ), more than a fourfold reduction in treatment failure rate (5.9% vs 26%; p<0.001 ) and less than a half of mortality rate compared to patients who received a non-bedaquiline-based regimen. The bedaquiline survival and favourable outcome effect remained significant in HIV-infected patients (p<0.001). The second study showed that linezolid interruption was common in patients receiving a bedaquiline-based treatment regimen, and that system-specific toxicity occurred within predictable time frames. It also showed that anaemia (77.3% versus 7.3%; p<0.001), peripheral neuropathy (63.6% versus 14.6%; p=0.003), and optic neuritis (18.2% versus 9.8%; p=0.34) occurred more frequently in linezolid interrupters than in non-interrupters. The third study showed that the use of delamanid-bedaquiline combination regimen was safe and efficacious in drug resistant TB patients with poor prognosis when compared with outcomes in the less sick patients who received a bedaquiline-based regimen. It also showed no significant difference in culture conversion rate at 6 months (92.5% versus 81.8%; p=0.26) or favourable treatment outcome rate (63.4% versus 67.5%; p=0.66) between the two groups. Although patients who received the combination regimen had more frequent occurrence of QTcF prolongation greater than 60 ms from baseline (p=0.001) and more episodes of QTcF greater than 450 ms during treatment (p=0.001), none of them were symptomatic or had delamanid or bedaquiline withdrawn from their regimen. Conclusion: These data demonstrated that new and repurposed drugs remarkably improved treatment outcomes in patients with drug-resistant TB. Although linezolid, which is an important component of the bedaquiline-based treatment regimen, is often associated with system-specific adverse events, these occurred at predictable time frames thereby guiding physicians to make informed management decisions. Lastly, drug resistant TB patients with poor prognosis may benefit from a regimen containing delamanid and bedaquiline which seems relatively safe from an adverse event perspective. These data, despite some limitations, make a case for a widespread and accelerated roll-out of new and repurposed drugs for the treatment of drug resistant TB.
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2

Hervieu, Laura. "Dévelοppement et évaluatiοn de nanοvecteurs pοur l'administratiοn οrale de fénοldοpam en vue du traitement de la pοlykystοse rénale autοsοmique dοminante". Electronic Thesis or Diss., Normandie, 2024. http://www.theses.fr/2024NORMR100.

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La polykystose rénale autosomique dominante (PKRAD) est une maladie héréditaire caractérisée par la présence de kyste au niveau des reins et par des atteintes cardiovasculaires. Elle est responsable d’environ 5 à 10 % des insuffisances rénales terminales. Il n’existe, à l’heure actuelle, aucun traitement permettant la prise en charge thérapeutique des atteintes rénales et cardiovasculaires de la PKRAD. Elle se caractérise par un dysfonctionnement des polycystines au niveau des cils des cellules endothéliales vasculaires et tubulaires rénales jouant un rôle dans la détection de stimuli mécanique. De nombreux travaux ont mis en évidence l’intérêt thérapeutique de la stimulation des récepteurs dopaminergiques de type 5 (D5), permettant de restaurer la mécanosensibilité des cellules endothéliales. Parmi les agonistes dopaminergiques, le fénoldopam se démarque de par sa sélectivité des récepteurs D5. Toutefois ses propriétés physicochimiques, en particulier sa faible demi-vie et sa sensibilité au métabolisme, en font une molécule peu adaptée à une administration per os, voie privilégiée dans le cas des maladies chroniques. Dans ce contexte, le fénoldopam a fait l’objet d’une formulation sous forme de nanoémulsions et de liposomes. Ces 2 formulations ont permis l’encapsulation de fénoldopam. Si les nanoémulsions ont montré une instabilité dans les milieux biomimétiques, confirmée par l’absence d’amélioration du profil pharmacocinétique, les liposomes, quant à eux se sont montrés plus stables. Ils ont également permis de modifier le devenir du fénoldopam, en comparaison à sa forme libre en solution, après administration par voie orale, laissant présager la possibilité d’obtenir une libération prolongée
Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by the presence of cysts in the kidneys and associated cardiovascular complications. It is responsible for about 5 to 10% of end-stage renal failure cases. Currently, there is no treatment available for the therapeutic management of renal and cardiovascular complications of ADPKD. The disease is characterized by dysfunction of polycystins in the cilia of vascular endothelial and renal tubular cells, which play a role in detecting mechanical stimuli. Numerous studies have highlighted the therapeutic potential of stimulating dopamine type 5 receptors (D5), which can restore the mechanosensitivity of endothelial cells. Among dopamine agonists, fenoldopam stands out due to its selectivity for D5 receptors. However, its physicochemical properties, particularly its short half-life and sensitivity to metabolism, make it poorly suited for oral administration, a preferred route for chronic diseases. In this context, fenoldopam has been formulated into nanoemulsions and liposomes. Both formulations allowed for the encapsulation of fenoldopam. While the nanoemulsions showed instability in biomimetic media, confirmed by the lack of improvement in the pharmacokinetic profile, the liposomes demonstrated greater stability. They also modified the fate of fenoldopam compared to its free form in solution after oral administration, suggesting the possibility of achieving prolonged release
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3

Hou, Chun-Li, and 侯君里. "The pan-Aurora kinase inhibitor tozasertib as a repurposed drug for Mycn-amplified neuroblastoma." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/91763913618808780304.

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4

Chung, Feng-Hsiang, and 鍾豐翔. "A Framework for Searching for Repurposed Drug Compounds for Systems Treatment of Complex Diseases: An Application to Colorectal Adenocarcinoma." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/8249tv.

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Анотація:
博士
國立中央大學
系統生物與生物資訊研究所
102
Drug repurposing has become an increasingly attractive approach to drug development owing to the ever-growing cost of new drug discovery and frequent withdrawal of successful drugs caused by side effect issues. Cancer is now recognized as is a systems disease caused by the breakdown of a large part of the cellular system, not just of the failure of one or two genes. Therefore, one cannot expect cancer to be effectively treated by one or a few single-target drugs. Here, we devised Functional Module Connectivity Map (FMCM) for the discovery of repurposed drug compounds for systems treatment of complex diseases, and applied it to colorectal adenocarcinoma. FMCM used multiple functional gene modules to query the Connectivity Map (CMap). The functional modules were built around hub genes identified, through the Gene Selection by Trend-of-disease-Progression (GSToP) procedure, from condition-specific gene-gene interaction networks constructed from sets of cohort gene expression microarrays. The formulated drug compounds were restricted to drugs exhibiting predicted minimal intracellular harmful side effects. Genes selected by GSToP had a much higher cancer gene hit rate (~50%) than that obtained by eBayes and SAM (~20%). We tested FMCM against the common practice of selecting drugs by using a single set of individual genes to query CMap (IGCM), and found that FMCM have higher robustness, accuracy, and reproducibility in identifying known anti-cancer agents. Among the 46 drugs selected by FMCM for colorectal adenocarcinoma, 65% had literature support for association with anti-cancer activities, and three drugs predicted to have adverse harmful effects on cancers had also been reported. In cell viability tests, we validated four candidate drugs: GW-8510, etacrynic acid, ginkgolide A, and 6-azathymine, as having high inhibitory activities against cancer cells. Through microarray experiments we confirmed the novel functional links predicted for three candidate drugs: phenoxybenzamine (broad effects), GW-8510 (cell cycle), and imipenem (immune system). We expect FMCM can be widely applied to repurposed drug discovery for systems treatment of other complex diseases.
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5

Pacheco, Mariana Carvalho Dias Brutt. "Demethylation of the epigenetically silenced androgen receptor gene by a repurposed drug in castration-resistant prostate cancer cell lines." Master's thesis, 2019. https://hdl.handle.net/10216/124744.

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6

Pacheco, Mariana Carvalho Dias Brutt. "Demethylation of the epigenetically silenced androgen receptor gene by a repurposed drug in castration-resistant prostate cancer cell lines." Dissertação, 2019. https://hdl.handle.net/10216/124744.

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7

Stylianou, Marios. "Pharmaceutical And Immunollogical Challenge Of Fungal Pathogens." Doctoral thesis, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-107713.

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Incidences of fungal infections are on the rise in immunosuppressed people. Predominant causative agents for these mycoses are species of the genus Candida, including Candida albicans, Candida glabrata and Candida dublieniensis. Despite a wide range of emerging pathogens, C. albicans remains the leading cause. According to recent epidemiological studies, blood stream infections with C. albicans cause annually ~55% mortality in approximately 300,000 patients from intensive care units worldwide. Furthermore, the percentage of morbidity linked to oral, esophageal and vulvovaginal mycoses cause by C. albicans reach up to 90%. Reasons for these medical concerns are the lack of efficient diagnostics and antifungal therapy. Here, we therefore sought to find novel antifungal strategies inspired by innate immune cells, such as neutrophils. These phagocytes are able to block the fungal pathogenicity. Neutrophils are bloodstream leukocytes serving as the first line of defense against pathogenic microbes. It has been shown that neutrophils have a strong antifungal activity by impairing the conversion of the dimorphic C. albicans from yeast to hyphal form (Y-H). Consequently, we raised the question whether other immune cells, such as mast cells, with less phagocytic cabapilities may have similar activity to neutrophils. Mast cells are tissue-dwelling cells. Mucosal tissue is rich in mast cells and usually constitutes the entry ports for fungal pathogens into the human body. A contribution of mast cells in antifungal defense is, thus, very likely. We human explored mast cell functions upon encounter with fungal pathogens. Interestingly, human mast cells show a transient potential to impair fungal viability. To understand the mechanism behind this impairment we analyzed the human mast cell functions in more detail. We found that human mast cells challenged with C. albicans, immediately degranulate and secrete distinct cytokines and chemokines in an orchestrated manner. The chemokines secreted attract neutrophils. Mast cells moreover are able to internalize fungal cells and to ‘commit suicide’ by releasing extracellular DNA traps that ensnare the pathogen.   The effectiveness of future antifungals is depended on targeting the pathogen virulence with more efficiency. The dimorphism of C. albicans is proven to be essential its virulence. Blockage of this switching ability could render the pathogen avirulent. Consequently, we screened for compounds that mimic the neutrophils anti-dimorphic activity by screening small chemical molecule libraries that block Y-H transition. The screening of big chemical libraries requires a reliable, reproducible and rapid high-throughput screening assay (HTS). We developed an HTS assay based on automated microscopy and image analysis, thereby allowing to distinguish between yeast and filamentous forms. In order to find the ideal Y-H blocker, we also evaluated the cell viability via the count of ATP levels when challenged with the respective small chemical molecules.   Drug development is an elaborate and expensive process. We therefore applied our screening setup to identify antidimorphic/antifungal activity in compounds from two different chemical libraries including FDA-approved drugs. The study disclosed 7 off-patent antifungal drugs that have potent antimycotic activity, including 4 neoplastic agents, 2 antipsychotic drugs and 1 antianemic medication. In a nutshell, we aimed to mimic the anti-dimorphic/antifungal activity of neutrophils with small chemical molecules. Furthermore, we elucidated how immune cells contribute to antifungal defense to exploit these mechanisms for the development of novel antifungal therapies. Thus, this thesis provides novel tools for the discovery of more efficient compounds, identifies previously unknown antifungal aspect of off-patent FDA-approved drugs and highlights the interplay of mast cells with pathogenic fungi with the aim to define new screening strategies.
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Книги з теми "Repurposed drug"

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Starving Cancer and Viruses with Commonly-Prescribed Pills: The Repurposed Drug Revolution. hope pressworks international, 2020.

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Repurposed Drugs for Cancer [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.91884.

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Singh, Pankaj Kumar, Dharmendra Kumar Khatri, Shashi Bala Singh, and Anitha Sriram, eds. An Update on SARS-CoV-2: Damage-response Framework, Potential Therapeutic Avenues and the Impact of Nanotechnology on COVID-19 Therapy Volume 1. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/97898150398631220101.

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This update on SARS-CoV-2 focuses on basic knowledge about the virus and COVID-19 treatment. Chapters present basic information about the disease and its treatment. The virology, epidemiology, etiology, and damage response framework of SARS-CoV-2 are also discussed in detail. The book also covers recent topics of interest to pharmacology scholars such as the immunopathogenesis of SARS-CoV2, nanotechnology, repurposed drug treatments, COVID-19 vaccines, and phytomedicine for COVID-19 therapeutics. Readers in pharmacology, virology and medicine will find the book a simple, yet informative update on SARS-CoV-2 and COVID-19 treatment.
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Parihar, Suraj P., Shashank Gupta, Makram Essafi, Bibhuti Mishra, and Ramandeep Singh, eds. Repurposed Drugs as Immune- Modulators to Combat Infectious Diseases. Frontiers Media SA, 2022. http://dx.doi.org/10.3389/978-2-88974-370-4.

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Campos-Parra, Alma D., Carlos Pérez-Plasencia, Teresita Padilla-Benavides, and Eduardo López-Urrutia, eds. Repurposed Drugs Targeting Cancer Signaling Pathways: Clinical Insights to Improve Oncologic Therapies. Frontiers Media SA, 2021. http://dx.doi.org/10.3389/978-2-88971-239-7.

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Hwang, Young-Hwan, and York Pei. Autosomal dominant polycystic kidney disease management. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0309_update_001.

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Management of patients with autosomal dominant polycystic kidney disease (ADPKD) currently comprises non-specific measures including promotion of healthy lifestyle, optimization of blood pressure control, and modification of cardiovascular risk factors. A high water intake of 3–4 L per day in patients with glomerular filtration rate greater than 30 mL/min/1.73 m2 may decrease the risk of kidney stones, but its potential benefit in reducing renal cyst growth is presently unproven. Maintenance of a target blood pressure of 130/80 mmHg is recommended by expert clinical guidelines though this is unlikely to slow cyst growth. It is unclear whether pharmacological blockade of the renin–angiotensin axis confers an extrarenal protective effect. Recognition of the variable clinical presentations of cyst infection, cyst haemorrhage, or nephrolithiasis is important for early diagnosis and optimal management of these complications. Most patients with ADPKD do well on dialysis and after transplantation. Nephrectomy may be needed to make space for a donor kidney, or if kidney size or infection is an issue after end-stage renal failure is reached. Recent advances in ADPKD have led to the identification of multiple potential therapeutic targets with more than 10 clinical trials completed or currently in progress. Given the promising results of the TEMPO trial, tolvaptan may well be the first disease-modifying drug to be approved for clinical use. Several other classes of drugs (e.g. somatostatin analogues, triptolide, metformin, and glucosylceramide synthase inhibitors) with good long-term safety profiles are promising candidates which may be repurposed for this disease. In the future, identifying patients with different risks of renal disease progression by their genotype and/or kidney volume will likely assume an important role for the clinical management of ADPKD.
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Campos-Parra, Alma D., Carlos Pérez-Plasencia, Teresita Padilla-Benavides, and Eduardo López-Urrutia, eds. Repurposed Drugs Targeting Cancer Signaling Pathways: Dissecting New Mechanisms of Action Through in vitro and in vivo Analyses. Frontiers Media SA, 2021. http://dx.doi.org/10.3389/978-2-88971-716-3.

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Hudson, Dale. Terrorist Vampires: Religious Heritage or Planetary Advocacy. Edinburgh University Press, 2018. http://dx.doi.org/10.3366/edinburgh/9781474423083.003.0007.

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This chapter unpacks depictions of US foreign policy in Hollywood blockbusters, franchises, and series, whose content was repurposed and production was often offshored. Vampire hunters perform the racialized warfare of the failed War on Drugs and ongoing War on Terror. Vampires advocate for planetary consciousness after neoliberalism’s ascendancy. Bram Stoker’s Dracula (1992), From Dusk till Dawn (1995), and Vampires (1998) organize fears of so-called Islamic fundamentalists and Mexican border hoppers. Deterritorialized biological warfare also manifests in films that return to the historical trauma of mixed blood via stories of mixed species in franchises like Blade (1998–2004) and Underworld (2003–2016) and series like True Blood (2008–2014), The Vampire Diaries (2009–present), and The Originals (2013–present). Others examine resilience through multiple conquests, as in Cronos (1992) set in México’s federal district and released on the quincentennial of Columbus’s conquest. Meanwhile, the Twilight franchise (2008–2012) christianizes the figure of the vampire and, by extension, the concept of the US secular democracy, but also evokes indigenous rights to land. Films ask us to find a space for empathy amidst the terror of economic and military violence.
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Частини книг з теми "Repurposed drug"

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Patil, Ruchira, Harshad Takate, Gaurav Shanbhag, Harshada Kiran Sonawane, Amruta Prabhakar Padakanti, and Naveen Chella. "Clinical Trials on Repurposed Drugs: An Overview." In Drug Repurposing, 173–99. Singapore: Springer Nature Singapore, 2024. http://dx.doi.org/10.1007/978-981-97-5016-0_9.

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Reaume, Andrew G., and Christopher A. Lipinski. "Chapter 10. Preclinical. A Repurposed Novel Lyn Kinase Activator, MLR-1023, is a Model Example of Pharmacological Pleiotropy." In Drug Repurposing, 196–220. Cambridge: Royal Society of Chemistry, 2022. http://dx.doi.org/10.1039/9781839163401-00196.

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Chopra, Simran, Aditya Dahiya, Ashrit Nair, Navneet Sharma, and Rakesh Kumar Sharma. "2-Deoxy-d-Glucose: A Repurposed Drug for COVID-19 Treatment." In Drug Repurposing for Emerging Infectious Diseases and Cancer, 479–500. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-19-5399-6_20.

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Dahiya, Mini, Anil Kumar, Monu Yadav, Pratibha Dhakla, and Shiva Tushir. "Therapeutic Targeting of Antineoplastic Drugs in Alzheimer’s Disease: Discovered in Repurposed Agents." In Drug Repurposing for Emerging Infectious Diseases and Cancer, 329–45. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-19-5399-6_15.

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Gautam, Rupesh K., Ritu Mishra, Kanika Sharma, and Manju Sharma. "Cellular and Molecular Mechanisms of Repurposed Antidiabetic Drug as an Adjunctive Treatment for Tuberculosis." In Targeting Cellular Signalling Pathways in Lung Diseases, 355–72. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-33-6827-9_15.

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Cervantes, Duilio, and Aida Adlimoghaddam. "Repurposed Drugs." In Small Molecules in Neurodegeneration, 137–50. Boca Raton: CRC Press, 2025. https://doi.org/10.1201/9781003520610-8.

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Arrowsmith, John, and Richard Harrison. "Drug Repositioning: The Business Case and Current Strategies to Repurpose Shelved Candidates and Marketed Drugs." In Drug Repositioning, 7–32. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2012. http://dx.doi.org/10.1002/9781118274408.ch1.

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Morasso, Stefano, Elisa Costanzi, Nicola Demitri, Barbara Giabbai, and Paola Storici. "The Role of Structural Biology Task Force: Validation of the Binding Mode of Repurposed Drugs Against SARS-CoV-2 Protein Targets." In Exscalate4CoV, 51–59. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-30691-4_7.

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Dhir, Neha, Ashish Jain, Dhruv Mahendru, Ajay Prakash, and Bikash Medhi. "Drug Repurposing and Orphan Disease Therapeutics." In Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.91941.

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Drug repurposing (or drug repositioning) is an innovative way to find out the new indications of a drug that already exists in the market with known therapeutic indications. It offers an effective way to drug developers or the pharmaceutical companies to identify new targets for FDA-approved drugs. Less time consumption, low cost and low risk of failure are some of the advantages being offered with drug repurposing. Sildenafil (Viagra), a landmark example of a repurposed drug, was introduced into the market as an antianginal drug. But at present, its use is repurposed as drug for erectile dysfunction. In a similar way, numerous drugs are there that have been successfully repurposed in managing the clinical conditions. The chapter would be highlighting the various drug repurposing strategies, drugs repurposed in the past and the current status of repurposed drugs in the orphan disease therapeutics along with regulatory guidelines for drug repurposing.
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T. Galatage, Sunil, Arehalli S. Manjappa, Raghwendra R. Waghmode, Swapnil S. Harale, Rushikesh B. Katkar, Sujit A. Desai, Swapnil S. Chopade, et al. "Role of Drug Repurposing in Cancer Treatment and Liposomal Approach of Drug Targeting." In Drug Repurposing - Advances, Scopes and Opportunities in Drug Discovery [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.110105.

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Cancer is the leading cause of death, and incidences are increasing significantly and patients suffering from it desperately need a complete cure from it. The science of using an already-invented drug that has been approved by the FDA for a new application is known as “drug repurposing.” Currently, scientists are drawn to drug repositioning science in order to investigate existing drugs for newer therapeutic uses and cancer treatment. Because of their unique ability to target cancer cells, recently repurposed drugs and the liposomal approach are effective in the treatment of cancer. Liposomes are nanovesicles that are drastically flexible, rapidly penetrate deeper layers of cells, and enhance intracellular uptake. More importantly, liposomes are biocompatible, biodegradable; entrap both hydrophobic and hydrophilic drugs. This chapter summarizes various approaches to drug repurposing, as well as drug repurposing methods, advantages and limitations of drug repurposing, and a liposomal approach to using repurposed drugs in cancer targeting. This chapter also summarizes liposomal structure, drug loading, and the mechanism of liposomes in targeted cancer treatment. The lipid-based liposomal approach is emerging as a powerful technique for improving drug solubility, bioavailability, reducing side effects, and improving the therapeutic efficacy of repurposed drugs for cancer treatment.
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Тези доповідей конференцій з теми "Repurposed drug"

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Ding, Yi, Ruiyang Gong, Juzhen Bai, Ruizhi Ou, and Zimeng Wu. "CTAG using GNN for GWAS analyses of schizophrenia to identify disease-associated genes and repurpose drugs." In 2024 Fourth International Conference on Biomedicine and Bioinformatics Engineering (ICBBE 2024), edited by Pier Paolo Piccaluga, Ahmed El-Hashash, and Xiangqian Guo, 21. SPIE, 2024. http://dx.doi.org/10.1117/12.3044175.

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Cavalla, David. "Commercialising drug repurposed products: what works and what doesn’t." In RExPO24. REPO4EU, 2024. http://dx.doi.org/10.58647/rexpo.24010.

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Evankovich, J., J. Villandre, T. Lear, Y. Chen, F. Tuncer, V. White, D. Camarco, Y. Liu, and B. Chen. "A Repurposed Drug Screen for Compounds Regulating Aquaporin 5 Stability in Lung Epithelial Cells." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4388.

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Evankovich, J., J. Villandre, V. White, T. Lear, Y. Chen, F. Tuncer, K. Lockwood, D. Camarco, Y. Liu, and B. Chen. "A Repurposed Drug Screen for Compounds Regulating Aquaporin 5 Stability in Lung Epithelial Cells." In American Thoracic Society 2022 International Conference, May 13-18, 2022 - San Francisco, CA. American Thoracic Society, 2022. http://dx.doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3254.

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Yadav, Anjali, Shraddha Bhutkar, and Vikas Dukhande. "Metabolic Rewiring and Mechanism of Action of an Antiepileptic Drug Repurposed for its Potential in Glioblastoma." In ASPET 2023 Annual Meeting Abstracts. American Society for Pharmacology and Experimental Therapeutics, 2023. http://dx.doi.org/10.1124/jpet.122.291070.

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Rabbani, Naila, Paul John Thornalley, Maryam Al-Motawa, and Mingzhan Xue. "Vulnerabilities of the SARS-Cov-2 Virus to Proteotoxicity – Opportunity for Repurposed Chemotherapy of COVID-19 Infection." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0291.

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The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 Coronavirus, has produced an urgent requirement and search for improved treatments whilst effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: Reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. We examined activated arginine residues in functional domain with predicted low pKa by neighboring group interaction in the SARS-CoV-2. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-COV and MERS. We also screened and identified drugs, which increase cellular MG concentration to virucidal levels and found two antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel were the best candidate for repurposing. Our findings provide evidence of potential vulnerability of SARS-CoV2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.
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Papineni, Rao V., Shahid Umar, Alexey Goltsov, and Ishfaq Ahmed. "Abstract LB-012: Deoxyglucose and bisphosphonate shows common pathways in its drug repurposed anticancer and anti-infection actions." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-lb-012.

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Fahal, AH, ES Ahmed, SM Bakhiet, OE Bakheet, LA Fahal, AA Mohamed, ESW Mohhamedelamin, et al. "Once-weekly repurposed fosravuconazole versus daily itraconazole, with surgery, in patients with eumycetoma in Sudan: a randomised, double-blind, phase 2, proof-of-concept superiority trial." In MSF Scientific Days International 2024. NYC: MSF-USA, 2024. http://dx.doi.org/10.57740/jznxuiaji7.

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INTRODUCTION Treatment options for the highly neglected fungal tropical disease eumycetoma are limited and poorly adapted to patients’ contexts, with surgery often required. The first-line treatment, itraconazole, thought to be 40% effective, must be taken twice daily for ≥12 months with food, making adherence difficult. An effective, affordable, context-appropriate treatment is urgently needed. The Drugs for Neglected Diseases Initiative (DNDi) repurposed the broad-spectrum antifungal agent fosravuconazole, developed by Eisai Ltd for onychomycosis. We aimed to compare two different doses of weekly fosravuconazole with standard-of-care daily itraconazole in patients with eumycetoma. METHODS This phase 2, randomised, double-blind, active-controlled, superiority trial was done at the Mycetoma Research Centre, Soba University Hospital, Sudan. Patients aged ≥15 years with a small-to-medium lesion (≥2 to <16 cm) caused by M mycetomatis requiring surgery were randomly assigned (1:1:1) to receive either 300 mg fosravuconazole weekly (group 1), 200 mg fosravuconazole weekly (group 2), or 400 mg itraconazole daily (group 3), for 12 months, together with surgery at 6 months in all groups. The primary efficacy endpoint, assessed in all patients receiving at least one dose of study drug (modified intention to treat), was complete cure at 12 months (absence of eumycetoma mass and sinuses and discharge with normal imaging; or a negative fungal culture if mass present). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT03086226). RESULTS Between 9 May, 2017, and 10 June, 2021, 104 patients were randomised (34 to group 1, 34 to group 2, and 36 to group 3).Median age was 29.0 (IQR22.0–33.0), 23.0 (20.0–29.0) and 24.5 (19.5–33.0) years for Groups 1, 2, and 3 respectively. Complete cure rates at end of treatment were 50.0% (95% CI 32.4–67.6), 64.7% (46.5–80.3), and 75.0% (57.8–87.9) with Groups 1, 2 and 3, respectively, showing no superiority of fosravuconazole over the standard-of-care (p=0.030 for Group 2 vs Group 3; and p=0.347 for Group 1 vs Group 3; with significance level set at 0.022). Treatment-emergent adverse drug reactions were reported in one (3%) of 34 patients in group 2 (nausea or vomiting) and three (8%) of 36 patients in group 3 (cortisol decreased, QT prolonged). CONCLUSION Although not superior, fosravuconazole 200 mg seemed to have similar efficacy to itraconazole, coupled with advantages such as a weekly, not daily, administration, no food effect, and low risk for drug-drug interactions. An early access programme is under review by authorities in Sudan and a regulatory dossier and global access plan are under preparation.
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Chakravarti, Sayak, Suman Mazumder, Farnaz Hemmati, Farshad Amiri, Taraswi Mitra Ghosh, Ujjal Kumar Mukherjee, Panagiotis Mistriotis, et al. "Abstract 1354: Deciphering the functional basis of synergy between taxanes and TAK715: A novel repurposed drug candidate in treatment-refractory aggressive prostate cancer." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1354.

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Neal, Tristan, Nanyun Tang, George Reid, Sara Byron, Harshil Dhruv, and Michael Berens. "Abstract 2189: Evaluating efficacy of repurposed drugs in treatment of glioblastoma." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-2189.

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