A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity

Franz S. Gruber, Zoe C. Johnston, Christopher L. R. Barratt (Lead / Corresponding author), Paul D. Andrews

Research output: Contribution to journalArticle

1 Citation (Scopus)
14 Downloads (Pure)

Abstract

There is an urgent need to develop new methods for male contraception, however a major barrier to drug discovery has been the lack of validated targets and the absence of an effective high-throughput phenotypic screening system. To address this deficit, we developed a fully-automated robotic screening platform that provided quantitative evaluation of compound activity against two key attributes of human sperm function: motility and acrosome reaction. In order to accelerate contraceptive development, we screened the comprehensive collection of 12,000 molecules that make up the ReFRAME repurposing library, comprising nearly all the small molecules that have been approved or have undergone clinical development, or have significant preclinical profiling. We identified several compounds that potently inhibit motility representing either novel drug candidates or routes to target identification. This platform will now allow for major drug discovery programmes that address the critical gap in the contraceptive portfolio as well as uncover novel human sperm biology.
Original languageEnglish
Article numbere51739
Number of pages14
JournaleLife
Volume9
DOIs
Publication statusPublished - 28 Jan 2020

Keywords

  • Acrosome reaction
  • Contraception
  • Drug discovery
  • Phenotypic screening
  • Sperm motility
  • Spermatozoa

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