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These observations support the concept that the Kp system is a key lever to control reproduction and is a therapeutic target.

However, the use of the endogenous peptides has clear limits.

Nevertheless, depending on the dosing regimen, such type of analogs could also be used to stimulate the reproductive system.Surprisingly, however, this medicinal chemistry effort did not lead to a significant exploitation of these molecules to evaluate their stimulatory effect on reproductive activity.In our previous work we designed a series of Kp10 analogs and evaluated their capacity to stimulate the reproductive axis.When tested in vivo these analogs showed an enhanced pharmacological profile compared to Kp10, but the increase of LH and FSH secretion lasted only several hours.

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To be used in a preclinical proof of concept for reproduction, these molecules needed further refinement.In the present work we report the design and profiling of a new potent and selective Kp analog and its successful application to perform a preclinical proof of concept for ovulation stimulation and puberty advancement.

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