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.
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.
CatSper closed (no drilling)
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.
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.