AUTHOR=Rossetti Thomas , Ferreira Jacob , Ghanem Lubna , Buck Hannes , Steegborn Clemens , Myers Robert W. , Meinke Peter T. , Levin Lonny R. , Buck Jochen 

TITLE=Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1013845

DOI=10.3389/fphys.2022.1013845

ISSN=1664-042X

ABSTRACT=<p>In mammalian cells, 10 different adenylyl cyclases produce the ubiquitous second messenger, cyclic adenosine monophosphate (cAMP). Amongst these cAMP-generating enzymes, bicarbonate (HCO<sub>3</sub><sup>−</sup>)-regulated soluble adenylyl cyclase (sAC; ADCY10) is uniquely essential in sperm for reproduction. For this reason, sAC has been proposed as a potential therapeutic target for non-hormonal contraceptives for men. Here, we describe key sAC-focused <italic>in vitro</italic> assays to identify and characterize sAC inhibitors for therapeutic use. The affinity and binding kinetics of an inhibitor can greatly influence <italic>in vivo</italic> efficacy, therefore, we developed improved assays for assessing these efficacy defining features.</p>