ArticleInternational journal of molecular sciences2025
Strategies to Develop Na,K-ATPase-α4 Inhibitors as Male Contraceptives.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Male contraception remains an unmet need. Na,K-ATPase α4 (NKA α4), a specific Na⁺/K⁺ transporter of the sperm flagellum, is an attractive target for male contraception. NKA α4 is critical for sperm motility and fertility, and its deletion in male mice causes complete infertility. Our previous structure-activity relationship (SAR) studies on a cardenolide scaffold identified a highly selective, safe NKAα4 inhibitor, but its complex, heavily hydroxylated structure posed challenges for modification and optimization. To address this, we employed a structural simplification strategy to synthesize novel steroidal and non-steroidal analogs and examined their effects on NKAα4 inhibition and sperm motility. Both series reduced sperm motility (up to ~50%), with IC
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