Compounds Reducing Human Sperm Motility as Potential Nonhormonal Contraceptives Identified Using a High-Throughput Phenotypic Screening Platform
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.
Authors
- Sarah Martins da Silva (ORCID: https://orcid.org/0000-0003-2579-4866)
- Caroline Wilson (ORCID: https://orcid.org/0000-0001-9940-0052)
- Anthony Richardson (ORCID: https://orcid.org/0009-0005-3690-3409)
- Ian H. Gilbert (ORCID: https://orcid.org/0000-0002-5238-1314)
- Kevin D. Read (ORCID: https://orcid.org/0000-0002-8536-0130)
- Darren Edwards (ORCID: https://orcid.org/0000-0001-8245-8928)
- Neil R. Norcross (ORCID: https://orcid.org/0000-0001-8050-5217)
- Rachel Myles (ORCID: https://orcid.org/0009-0000-1667-5879)
- David P. Day (ORCID: https://orcid.org/0000-0002-8706-8053)
- Irene Georgiou (ORCID: https://orcid.org/0000-0002-6042-9816)
- Franz Gruber (ORCID: https://orcid.org/0000-0003-2008-8460)
- Zoe C Johnston (ORCID: https://orcid.org/0000-0003-0904-7166)
- Christopher L. R. Barratt (ORCID: https://orcid.org/0000-0003-0062-9979)
- Jason R. Swedlow (ORCID: https://orcid.org/0000-0002-2198-1958)
- Halimatu Joji
Institutions
- University of Dundee (GB)
- Discovery Centre (CA)
- Ninewells Hospital (GB)
- National Phenotypic Screening Centre (GB)
- Wellcome Centre for Anti-Infectives Research (GB)
- Drug Discovery Laboratory (Norway) (NO)
- Institut de Biologie Moléculaire et Cellulaire (FR)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1021/acsomega.5c08336
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00