Compounds reducing human sperm motility as potential non hormonal contraceptives identified using a high-throughput phenotypic screening platform

TY - JOUR

T1 - Compounds reducing human sperm motility as potential non hormonal contraceptives identified using a high-throughput phenotypic screening platform

AU - Richardson, Anthony

AU - Gruber, Franz S.

AU - Day, David P.

AU - Edwards, Darren

AU - Georgiou, Irene

AU - Johnston, Zoe C.

AU - Joji, Halimatu

AU - Martins Da Silva, Sarah

AU - Myles, Rachel

AU - Norcross, Neil R.

AU - Read, Kevin D.

AU - Swedlow, Jason R.

AU - Wilson, Caroline

AU - Barratt, Christopher L. R.

AU - Gilbert, Ian H.

PY - 2025/11/27

Y1 - 2025/11/27

N2 - 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.

AB - 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.

U2 - 10.1021/acsomega.5c08336

DO - 10.1021/acsomega.5c08336

M3 - Article

C2 - 41502742

SN - 2470-1343

VL - 10

SP - 59121

EP - 59134

JO - ACS Omega

JF - ACS Omega

IS - 48

ER -