The past century has been characterized by intensive efforts, within both academia and the pharmaceutical industry, to introduce new treatments to individuals with rheumatic autoimmune inflammatory diseases (RAIDs), often by 'borrowing' treatments already employed in one RAID or previously used in an entirely different disease, a concept known as drug repurposing. However, despite sharing some clinical manifestations and immune dysregulation, disease pathogenesis and phenotype vary greatly among RAIDs, and limited understanding of their aetiology has made repurposing drugs for RAIDs challenging. Nevertheless, the past century has been characterized by different 'waves' of repurposing. Early drug repurposing occurred in academia and was based on serendipitous observations or perceived disease similarity, often driven by the availability and popularity of drug classes. Since the 1990s, most biologic therapies have been developed for one or several RAIDs and then tested among the others, with varying levels of success. The past two decades have seen data-driven repurposing characterized by signature-based approaches that rely on molecular biology and genomics. Additionally, many data-driven strategies employ computational modelling and machine learning to integrate multiple sources of data. Together, these repurposing periods have led to advances in the treatment for many RAIDs.
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http://dx.doi.org/10.1038/s41584-019-0337-0 | DOI Listing |
Viruses
January 2025
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.
View Article and Find Full Text PDFViruses
January 2025
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.
View Article and Find Full Text PDFPharmaceutics
January 2025
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
: Tamoxifen (TAM) is an anti-breast cancer drug suffering from acquired resistance development, prompting cancer relapse. Propranolol (PRO)'s repurposing for cancer therapy has gained interest. This work aimed to investigate combined TAM/PRO therapy for potentiating the anti-breast cancer activity of TAM.
View Article and Find Full Text PDFPharmaceutics
January 2025
Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, 70125 Bari, Italy.
: Since 2008, following clinical studies conducted on children that revealed the ability of the β-adrenergic antagonist propranolol to inhibit capillary growth in infantile hemangiomas (IHs), its oral administration has become the first-line treatment for IHs. Although oral propranolol therapy at a dosage of 3 mg/kg/die is effective, it can cause systemic adverse reactions. This therapy is not necessarily applicable to all patients.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Background/objectives: Septic cardiomyopathy (SCM) is a severe cardiac complication of sepsis, characterized by cardiac dysfunction with limited effective treatments. This study aimed to identify repurposable drugs for SCM by integrated multi-omics and network analyses.
Methods: We generated a mouse model of SCM induced by lipopolysaccharide (LPS) and then obtained comprehensive metabolic and genetic data from SCM mouse hearts using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and RNA sequencing (RNA-seq).
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