Drug repurposing: progress, challenges and recommendations

Pushpakom, Sudeep; Iorio, Francesco; Eyers, Patrick A.; Escott, Katherine J.; Hopper, Shirley; Wells, Andrew D.; Doig, Andrew J.; Guilliams, Tim; Latimer, Joanna Elizabeth; McNamee, Christine J.; Norris, Alan; Sanséau, Philippe; Cavalla, David; Pirmohamed, Munir

doi:10.1038/nrd.2018.168

Cited by 3,363 publications

(2,809 citation statements)

References 142 publications

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“…This paradigm was based on the observation that different viruses utilize similar pathways and host factors to replicate inside a cell (Bosl et al, 2019). Although the concept of BSAAs has been around for almost 50 years, the field received a new impetus with recent outbreaks of Ebola, Zika, Dengue, influenza and other viral infections, the discovery of novel host-directed agents as well as development of drug repositioning methodology.Drug repurposing, also called repositioning, redirecting, reprofiling, is a strategy for generating additional value from an existing drug by targeting disease other than that for which it was originally intended (Nishimura and Hara, 2018;Pushpakom et al, 2019). This has significant advantages over new drug discovery since chemical synthesis steps, manufacturing processes, reliable safety, and pharmacokinetic properties in pre-clinical (animal model) and early clinical developmental phases (phase 0, I and IIa) are already available (Figure 1).…”

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confidence: 99%

“…Drug repurposing, also called repositioning, redirecting, reprofiling, is a strategy for generating additional value from an existing drug by targeting disease other than that for which it was originally intended (Nishimura and Hara, 2018;Pushpakom et al, 2019). This has significant advantages over new drug discovery since chemical synthesis steps, manufacturing processes, reliable safety, and pharmacokinetic properties in pre-clinical (animal model) and early clinical developmental phases (phase 0, I and IIa) are already available (Figure 1).…”

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confidence: 99%

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Discovery and development of safe-in-man broad-spectrum antiviral agents

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

198

108

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# Contributed equally J o u r n a l P r e -p r o o f Highlights  We reviewed discovery and development process of broad-spectrum antiviral agents.  We summarized the information on 119 safe-in-man agents in freely accessible database.  Further studies will increase the number of broad-spectrum antivirals, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections. Abstract: Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and reemerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. J o u r n a l P r e -p r o o f 2015). Antiviral drugs and vaccines are used to fight viral infections in human (De Clercq and Li, 2016; Marston et al., 2014). Previously, there has been a focus on "one drug, one virus" dogma, which relied on targeting virus-specific factors. A counterpoint to this is "one drug, multiple viruses" paradigm, which came with the discovery of broad-spectrum antiviral agents (BSAAs), small-molecules that inhibit a wide range of human viruses (Bekerman and Einav, 2015; de Clercq and Montgomery, 1983; Debing et al., 2015; Ianevski et al., 2019; Rada and Dragun, 1977; Sidwell et al., 1972). This paradigm was based on the observation that different viruses utilize similar pathways and host factors to replicate inside a cell (Bosl et al., 2019). Although the concept of BSAAs has been around for almost 50 years, the field received a new impetus with recent outbreaks of Ebola, Zika, Dengue, influenza and other viral infections, the discovery of novel host-directed agents as well as development of drug repositioning methodology. Drug repurposing, also called repositioning, redirecting, reprofiling, is a strategy for generating additional value from an existing drug by targeting disease other than that for which it was originally intended (Nishimura and Hara, 2018; Pushpakom et al., 2019). This has significant advantages over new drug discovery since chemical synthesis steps, manufacturing processes, reliable safety, and pharmacokinetic properties in pre-clinical (animal model) and early clinical developmental phases (phase 0, I and IIa) are already available (Figure 1). Therefore, repositioning of launched or even failed drugs to viral diseases provides unique translational opportunities, includi...

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confidence: 99%

mentioning

confidence: 99%

Discovery and development of safe-in-man broad-spectrum antiviral agents

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

198

108

View full text Add to dashboard Cite

show abstract

“…Drug repositioning circumvents the usual route of substantially higher rates, slow pace and side effects etc. [27][28][29]. It is becoming an attractive concept for pharmaceutical industries.…”

Section: Drug Repositioningmentioning

confidence: 99%

“…Repositioning of old drugs offer rapid transition from bench to bedside as already approved by FDA and other regulatory norms, passed through the clinical trials and are approved for human use. These drugs have well defined pharmacodynamics, pharmacokinetics, dose, side effects, metabolic profiles and targeted molecular pathway etc [29,34]. Here, the clinical development can directly start from the phase II trial to assess the efficacy for new indication/disease target.…”

Section: Drug Repositioningmentioning

confidence: 99%

Drug repurposing for breast cancer therapy: Old weapon for new battle

Aggarwal

Verma

Aggarwal

et al. 2021

Seminars in Cancer Biology

110

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Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed. Current breast cancer therapyUnlike a decade ago, clinicians today have multiple choices for breast cancer treatment depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient [9-13]. Chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery are the common modalities for breast cancer [10,14]. Primary choice of treatment usually includes surgery with the aim of complete resection of the major tumor mass on the first hand. Breast conserving (lumpectomy) and breast reconstruction surgeries, mastectomy or lymph node dissections are performed initially in the breast cancer patients [15]. Surgery may be preceded with the systemic neoadjuvant therapies in order to shrink the tumor for effective surgery and to maximize breast conservation. For example, in HER2+ cases, Trastuzumab (Herceptin) and Pertuzumab (Perjeta)

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“…Besides traditional biomedical experiments, such as binding assays and phenotypic screening, increasing numbers of in silico drug repurposing methods that use computational approaches to analyze available heterogeneous data are being used. Some of them have shown great promise, including genetic association analysis, pathway mapping, molecular docking, and signature profile matching (e.g., measuring similarity of drugs on chemical structures) for drug repurposing …”

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confidence: 99%

Electronic Health Records for Drug Repurposing: Current Status, Challenges, and Future Directions

Jiang

et al. 2020

Clin Pharma and Therapeutics

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Drug repurposing: progress, challenges and recommendations

Cited by 3,363 publications

References 142 publications

Discovery and development of safe-in-man broad-spectrum antiviral agents

Discovery and development of safe-in-man broad-spectrum antiviral agents

Drug repurposing for breast cancer therapy: Old weapon for new battle

Electronic Health Records for Drug Repurposing: Current Status, Challenges, and Future Directions

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