# Compounds Reducing Human Sperm Motility as Potential Nonhormonal Contraceptives Identified Using a High-Throughput Phenotypic Screening Platform

**Authors:** Anthony Richardson, Franz S. Gruber, David P. Day, Darren Edwards, Irene Georgiou, Zoe C. Johnston, Halimatu Joji, Sarah Martins da Silva, Rachel Myles, Neil R. Norcross, Kevin D. Read, Jason R. Swedlow, Caroline Wilson, Christopher L. R. Barratt, Ian H. Gilbert

PMC · DOI: 10.1021/acsomega.5c08336 · ACS Omega · 2025-11-27

## TL;DR

Researchers used a high-throughput screening method to find nonhormonal contraceptive compounds that reduce human sperm motility without harming other cells.

## Contribution

A phenotypic screening platform identified nonhormonal contraceptive candidates with reduced cytotoxicity.

## Key findings

- Nine chemical series were identified that selectively reduce sperm motility.
- No clinically progressable leads were found, but useful research tool compounds were identified.
- The study improved understanding of screening technology for contraceptive discovery.

## Abstract

In this article,
we detail our latest findings toward developing
a diversified series of potential nonhormonal contraceptive compounds
using a phenotypic screening approach against human sperm. Phenotypic
screening of nine compound libraries (88,773 compounds in total) was
conducted using an in-house automated robotic screening platform,
allowing quantification of sperm motility in samples pretreated with
the compounds. From these screens, 9 chemical series were identified
and investigated in hit expansion programs, with a particular focus
on identifying chemical matter that selectively reduces sperm motility
without any significant cytotoxicity in somatic cells (HepG2 cells).
While there were no clinically progressable leads identified, the
study did identify some useful tool compounds for research into the
fundamental biology underpinning nonhormonal contraceptive discovery,
and a lot was learned about the screening technology, which sets us
up for future screening to identify and develop better chemical starting
points.

## Linked entities

- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Diseases:** cytotoxicity (MESH:D064420)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12771125/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC12771125/full.md

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Source: https://tomesphere.com/paper/PMC12771125