‘99% effective in mice’ — scientists develop male contraceptive pill


Scientists in the United States (US) say they have developed a non-hormonal contraceptive pill for males.


The researchers from the University of Minnesota presented the results of their trial on Wednesday at the spring meeting of the American Chemical Society (ACS).


There are currently two effective birth control options for men — condoms and vasectomy.


According to a statement issued on the pill, Gunda Georg, head of the medicinal chemistry department at the university, said testing of the pill — YCT529 — which was found to be “99 percent effective in mice”, will be used in human clinical trials to begin in the third or fourth quarter of 2022.


“Because it can be difficult to predict if a compound that looks good in animal studies will also pan out in human trials, we’re currently exploring other compounds as well,” Georg said.


A statement by the ACS also noted that the pill, which limits chances of impregnating females, loses effect when no longer taken.


“To develop their non-hormonal male contraceptive, the researchers targeted a protein called the retinoic acid receptor alpha (RAR-α). This protein is one of a family of three nuclear receptors that bind retinoic acid, a form of vitamin A that plays important roles in cell growth, differentiation (including sperm formation) and embryonic development,” the statement reads.


“Knocking out the RAR-α gene in male mice makes them sterile, without any obvious side effects. Other scientists have developed an oral compound that inhibits all three members of the RAR family (RAR-α, -β and -γ) and causes reversible sterility in male mice, but Georg’s team and their reproductive biology collaborators wanted to find a drug that was specific for RAR-α and therefore less likely to cause side effects.


“So the researchers closely examined crystal structures of RAR-α, -β and -γ bound to retinoic acid, identifying structural differences in the ways the three receptors bind to their common ligand.


“With this information, they designed and synthesized approximately 100 compounds and evaluated their ability to selectively inhibit RAR-α in cells. They identified a compound, which was named YCT529, that inhibited RAR-α almost 500 times more potently than it did RAR-β and -γ.


“When given orally to male mice for 4 weeks, YCT529 dramatically reduced sperm counts and was 99% effective in preventing pregnancy, without any observable side effects. The mice could father pups again 4-6 weeks after they stopped receiving the compound.”

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