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Compounds Reducing Human Sperm Motility as Potential Nonhormonal Contraceptives Identified Using a High-Throughput
Anthony Richardson1, Franz S Gruber2, David P Day1
1Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, U.K.
ACS Omega
|January 8, 2026
Summary
Researchers screened 88,773 compounds for nonhormonal contraceptives. While no clinical leads emerged, the study identified tool compounds and improved screening technology for future contraceptive development.
Area of Science:
- Reproductive biology and pharmacology
- Drug discovery and development
Background:
- Developing nonhormonal contraceptives is crucial for reproductive health.
- Phenotypic screening offers a pathway to identify novel contraceptive agents.
Purpose of the Study:
- To identify potential nonhormonal contraceptive compounds using phenotypic screening.
- To investigate chemical series that selectively reduce sperm motility without cytotoxicity.
Main Methods:
- Phenotypic screening of 88,773 compounds across nine libraries using an automated robotic platform.
- Quantification of human sperm motility and assessment of cytotoxicity in HepG2 cells.
Main Results:
- Identification of 9 chemical series with effects on sperm motility.
- Selective reduction of sperm motility was a key criterion, alongside minimal cytotoxicity.
- No clinically progressable leads were identified in this screening round.
Conclusions:
- The study yielded valuable tool compounds for nonhormonal contraceptive research.
- Significant advancements were made in screening technology for future drug discovery.
- Further optimization and screening are needed to identify clinically viable contraceptive leads.

