Male, oral, non-hormonal
Women have a wide range of means for family planning, including oral contraceptives, patches, intrauterine devices, and this is partly why they bear more responsibility in case of unwanted pregnancy. But the possibilities of birth control for men may soon expand. At the spring meeting of the American Chemical Society (ACS), researchers reported on a non-hormonal male contraceptive that, in experiments on mice, effectively prevented pregnancy without obvious side effects.
Currently, only two effective methods of contraception are available to men: barrier (condoms) and vasectomy, both have disadvantages. The first is the most affordable and easiest method of contraception, and also protects against sexually transmitted infections, but condoms can break. In addition, some men are allergic to latex, which is part of standard condoms. The second is a surgical procedure that can be painful and involves risks accompanying any surgical intervention. In addition, vasectomy is almost irreversible. Therefore, men need a safe, effective, persistent, but reversible contraceptive, similar to birth control pills for women.
Abdullah Al Noman and his colleagues from the University of Minnesota are working on the creation of an oral contraceptive for men, focusing on the search for a non-hormonal remedy, since hormonal changes are accompanied by undesirable side effects. Most of the experimental compounds currently undergoing clinical trials are aimed at the male sex hormone testosterone, therefore they carry the risk of side effects such as weight gain, depression and an increase in the level of "bad" cholesterol (low-density lipoproteins).
The alpha retinoic acid receptor (RAR-α) was chosen as the target. This protein is a representative of a family of nuclear receptors that bind retinoic acid, a form of vitamin A necessary for cell growth and differentiation, including into spermatozoa. Switching off the RAR-α gene in male mice makes them sterile without any obvious side effects. There is already an oral compound that inhibits all three proteins of the RAR family (RAR-α, -β and -γ) and causes reversible sterility in male mice, but the research team was looking for a compound specific to RAR-α and therefore carries a lower risk of side effects.
To do this, the researchers studied the crystal structures of RAR-α, -β and -γ and found structural differences in the ways of binding to retinoic acid. They have developed and synthesized about 100 compounds that are more or less capable of selectively inhibiting RAR-α in cells. The experimental compound YCT529 inhibited RAR-α almost 500 times more strongly than RAR-β and RAR-γ.
The structural formula of the drug.
When administered orally to male mice for 4 weeks, YCT529 dramatically reduced the number of spermatozoa and was 99% effective in preventing pregnancy without any noticeable side effects. Even with a 100-fold excess of the effective dose, the compound showed no toxicity. The mice fully restored fertility 4-6 weeks after discontinuation of treatment.
The authors plan to start clinical trials of YCT529 in the third or fourth quarter of 2022. Currently, they are continuing to search for other RAR-α inhibitors in case YCT529 does not show the same efficacy and safety in men as in the experiment with mice.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the American Chemical Society: A non-hormonal pill could soon expand men's birth control options.