Asset

  • No.

    140

  • Asset Title

    Spermine Prodrugs for Treating Low Spermine Disorders

  • Organization

    University of Central Florida

  • Product Type

    Small molecule

  • Therapeutic Area

    Genitourinary disease

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    Snyder Robinson Syndrome (SRS) is a rare disease associated with a defective spermine synthase gene and low intracellular spermine levels. 

    • A spermine replacement therapy was developed using a spermine prodrug that enters cells via the polyamine transport system. The prodrug was comprised of three components: a redox-sensitive quinone “trigger”, a “trimethyl lock (TML)” aryl “release mechanism”, and spermine. The presence of spermine in the design facilitated uptake by the polyamine transport system. The quinone–TML motifs provided a redox-sensitive agent, which upon intracellular reduction generated a hydroquinone, which underwent intramolecular cyclization to release free spermine and a lactone byproduct. 

    • Most SRS fibroblasts treated with the prodrug revealed a significant increase in intracellular spermine. Administering the spermine prodrug through feeding in a Drosophila model of SRS showed significant beneficial effects. 

    • A spermine prodrug is developed and provides a lead compound for future spermine replacement therapy experiments. 

  • Patent

    US20210000769A1

  • Publication

    Development of a Redox-Sensitive Spermine Prodrug for the Potential Treatment of Snyder Robinson Syndrome. J Med Chem. (2021)

  • Attachment

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