Repurposing of the Drug Tezosentan for Cancer Therapy

Ribeiro, Eduarda; Vale, Nuno

doi:10.3390/cimb45060325

Cited by 6 publications

(3 citation statements)

References 83 publications

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“…Drug repurposing studies are promising for various diseases [ 27 , 28 , 29 , 30 ] and have been conducted to identify several active drugs against C. auris , such as iodoquinol [ 20 ], Miltefosine [ 20 , 31 ], Robenidine [ 32 ], Salicylanilide oxyclozanide [ 33 ], Pyrvinium pamoate [ 34 ], Broxyquinoline [ 18 ], Tamoxifen citrate [ 34 ], Alexidine dihydrochloride [ 18 , 35 ], AC- 93253 iodide [ 18 ], Chloroxine [ 18 ], Clioquinol [ 18 ], Sertraline [ 36 ], Rolipram [ 34 ], Trifluoperazine [ 34 ], dihydrochloride [ 34 ], Thiethylperazine dimalate [ 34 ], ebselen [ 19 , 34 ], Disulfiram [ 37 ], (−)- MK 801 hydrogen maleate [ 34 ], Suloctidil [ 34 ], Ciclopirox ethanolamine [ 34 ], and Guanadrel sulfate [ 34 ]. Nanomaterial-based studies and drug repurposing approaches have led to the proposal of several alternative drugs with C. aruis growth inhibition activity.…”

Section: Introductionmentioning

confidence: 99%

The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection

Borgio,

Almandil,

Selvaraj

et al. 2024

Pharmaceutics

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Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti-C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase–dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti-auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris, and significant (p-value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti-C. auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection.

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Section: Introductionmentioning

confidence: 99%

The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection

Borgio,

Almandil,

Selvaraj

et al. 2024

Pharmaceutics

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“…One promising avenue is the repurposing of existing drugs for anticancer purposes. Drug repurposing, also known as drug repositioning, involves identifying new therapeutic indications for drugs that have already been approved for other medical conditions [9,10]. By taking advantage of the existing pharmacological and safety profiles of these drugs, researchers can speed up the development of new anticancer therapies and potentially bypass the time-consuming and costly process of drug discovery and development [11,12].…”

Section: Introductionmentioning

confidence: 99%

Positive Inotropic Agents in Cancer Therapy: Exploring Potential Anti-Tumor Effects

Ribeiro,

Vale

2024

Targets

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Cancer remains a significant global health challenge despite advancements in diagnosis and treatment. Traditional cancer therapies often face limitations such as toxicity and drug resistance. Drug repurposing has emerged as a promising strategy to overcome these challenges by identifying new therapeutic uses for existing drugs. This review explores the potential of repurposing positive inotropic agents, which are traditionally used in cardiovascular medicine, for cancer therapy. Positive inotropic agents, including cardiac glycosides, β-agonists, phosphodiesterase inhibitors, and calcium sensitizers have shown preclinical evidence of anti-tumor activity through various mechanisms, such as modulation of the intracellular signaling pathways, increasing cyclic adenosine monophosphate (cAMP) levels, the production of nitric oxide, and decreasing reactive oxygen species levels. Despite the absence of specific clinical trials in this area, these findings suggest a promising avenue for further research and development of combination therapies to improve cancer treatment outcomes. However, challenges such as elucidating specific anti-tumor mechanisms, identifying predictive biomarkers, and optimizing safety profiles need to be addressed to fully realize the therapeutic potential of positive inotropic agents in oncology.

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“…Drug repurposing, also known as repositioning, reprofiling or re-tasking, revolves around the concept of discovering novel applications for drugs that have already gained approval [ 4 ]. The key to drug repurposing lies in the available knowledge about the bioavailability, pharmacokinetics, dosage, safety, efficacy and toxicity of these approved drugs [ 5 ].…”

Section: Introduction To Drug Repurposingmentioning

confidence: 99%

Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology

Ribeiro,

Vale

2023

Biomolecules

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Drug repurposing, also known as repositioning or reprofiling, has emerged as a promising strategy to accelerate drug discovery and development. This approach involves identifying new medical indications for existing approved drugs, harnessing the extensive knowledge of their bioavailability, pharmacokinetics, safety and efficacy. Levosimendan, a calcium sensitizer initially approved for heart failure, has been repurposed for oncology due to its multifaceted pharmacodynamics, including phosphodiesterase 3 inhibition, nitric oxide production and reduction of reactive oxygen species. Studies have demonstrated that levosimendan inhibits cancer cell migration and sensitizes hypoxic cells to radiation. Moreover, it exerts organ-protective effects by activating mitochondrial potassium channels. Combining levosimendan with traditional anticancer agents such as 5-fluorouracil (5-FU) has shown a synergistic effect in bladder cancer cells, highlighting its potential as a novel therapeutic approach. This drug repurposing strategy offers a cost-effective and time-efficient solution for developing new treatments, ultimately contributing to the advancement of cancer therapeutics and improved outcomes for patients. Further investigations and clinical trials are warranted to validate the effectiveness of levosimendan in oncology and explore its potential benefits in a clinical setting.

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Repurposing of the Drug Tezosentan for Cancer Therapy

Cited by 6 publications

References 83 publications

The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection

The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection

Positive Inotropic Agents in Cancer Therapy: Exploring Potential Anti-Tumor Effects

Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology

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