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      Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases

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          Abstract

          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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          The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics.

          Small-molecule compounds approved for use as drugs may be "repurposed" for new indications and studied to determine the mechanisms of their beneficial and adverse effects. A comprehensive collection of all small-molecule drugs approved for human use would be invaluable for systematic repurposing across human diseases, particularly for rare and neglected diseases, for which the cost and time required for development of a new chemical entity are often prohibitive. Previous efforts to build such a comprehensive collection have been limited by the complexities, redundancies, and semantic inconsistencies of drug naming within and among regulatory agencies worldwide; a lack of clear conceptualization of what constitutes a drug; and a lack of access to physical samples. We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening.
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            NCATS launches drug repurposing program.

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              Author and article information

              Journal
              Nature Reviews Rheumatology
              Nat Rev Rheumatol
              Springer Science and Business Media LLC
              1759-4790
              1759-4804
              December 12 2019
              Article
              10.1038/s41584-019-0337-0
              31831878
              0303ad54-266c-4093-9178-0bb8b0536cf6
              © 2019

              http://www.springer.com/tdm

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