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Lupeol is a plant-derived, non-hormonal compound that prevents fertilization.
 

When sperm approach an egg, sperm are triggered to change the way they move: sperm begin drilling through the egg's protective layers to reach the egg.

FERTILIZATION

Basal sperm motility
Hyperactivated sperm motility

Sperm drilling (known as hyperactivation) is driven by calcium ion influx through CatSper, a calcium channel found on sperm tails.

Activation of CatSper occurs once 2-arachidonoylglycerol (2AG) is removed from the sperm tail plasma membrane.

The amount of 2AG in the sperm tail plasma membrane is controlled by the activity of a progesterone (P4) receptor called ABHD2.

No progesterone:

ABHD2 inactive

CatSper closed (no drilling)

With progesterone:

ABHD2 active

CatSper open (drilling)

When progesterone binds to and activates ABHD2, it depletes 2AG from the surrounding area of membrane so CatSper activates and sperm begin to drill.

 

Lupeol also binds to ABHD2, but does not activate it.

Lupeol prevents progesterone from binding to ABHD2, which prevents CatSper activation and sperm drilling.

No sperm drilling means no fertilization.

FERTILIZATION

NO

FERTILIZATION

YourChoice Therapeutics is developing lupeol into a first-in-class non-hormonal contraceptive for women.

Lupeol is the basis to screen for more efficacious compounds from which we will develop a non-hormonal unisex contraceptive.

 

References

REVOLUTIONIZING BIRTH CONTROL

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