Characterization and Assessment of KCNU1/SLO3 as a Potential Non-hormonal Contraceptive Target

The Structural Genomics Consortium (SGC) has recently embarked on its first research project in reproductive biology as a part of the SGC’s new open science Women’s and Children’s Health Program (WCHP). This program, which was generously funded by the Bill & Melinda Gates Foundation will focus on drug discovery for childhood diseases and development as well as reproductive biology and disease. One of the first initiatives of WCHP is to identify and characterize protein targets for non-hormonal contraceptive agents.

Although most contraceptive strategies have focused on the female reproductive system, there is great interest in developing contraceptives for the male reproductive system. Ion channels in sperm are of interest as viable targets for non-hormonal contraceptives for several reasons. First, they are promising drug targets due to their involvement in various pathophysiologies as well as their roles in sperm capacitation and the acrosomal reaction. Second, they contain druggable sites at cell surfaces, and third, proteins that respond to ion signaling are essential to sperm cells which must adapt to changing environments and respond to cues from the female reproductive tract. It is worth noting that approximately 15% of current drug targets are ion channels. One potential target is potassium/calcium-activated channel subfamily U member I (KCNU1), sometimes referred to as SLO3, a potassium channel that is expressed solely in mammalian sperm. In this work, we will describe our efforts to characterize KCNU1 as a potential protein target for non-hormonal contraceptives.